bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated context-specific actions disrupt feedforward adjustments in motor commands in younger and older adults
Authors: Sager Catherine Anne , Diamond Ella , Hulsey-Vincent Miranda Rose , Marneweck Michelle
Published: April 2024

Adjusting planned actions in response to sensory stimuli degrades with age contributing to increased incidence of errors ranging from clumsy spills to catastrophic falls. Multiple factors likely contribute to age-related motor inflexibility, including sensory- and cognition-supporting system declines. Here, we present compelling evidence for repetition to disrupt feedforward adjusting of motor commands in younger and older adults, which suggests increases in stereotypy as a deleterious potentiator of motor control errors.
The Lived Experience of Play and How It Relates to Psychological Wellbeing: An Interpretive Phenomenological Analysis (IPA) Study Amongst Undergraduate Students from Medicine, Nursing, and Allied Health Professions’ Programmes in the United Kingdom
Authors: Rylance-Graham Rebecca
Published: April 2024

Current literature acknowledges that undergraduate students undertaking programmes in medicine, nursing, and allied health professions experience occupational stress which presents as a detriment to mental health, psychological wellbeing (PWB), and burnout. Strategies to improve the wellbeing of students have been slow to embed and have had limited impact, indeed the issue of declining wellbeing amongst this group is escalating. Studies from the business literature suggest that organisations that foster a playful environment reap benefits in terms of employee wellbeing. This interpretive phenomenological analysis (IPA) study explored the lived experiences of play amongst undergraduate students from medicine, nursing, and allied health professions’ programmes in the clinical practice setting. The resultant findings offer some unique empirical insights into the types of play that the students engaged in, ranging from informal banter with peers and patients to artful, sophisticated, cocreated play. The study also revealed insights about the factors which facilitate play, notably the “big personalities” on the ward. The factors which limited play are related to the tension between being a health professional and the enactment of play as well as hierarchical factors. Crucially, the study found that the practice of play induced key hedonic and eudaimonic PWB benefits to the students, ranging from positive affect to improved relationships, a sense of meaning, and a positive learning environment, offering original empirical insights. These findings have not been observed previously and shine a conceptual light on a previously unknown phenomenon.
Mathematical Model-Driven Deep Learning Enables Personalized Adaptive Therapy
Authors: Gallagher Kit , Strobl Maximilian A.R. , Park Derek S. , Spoendlin Fabian C. , Gatenby Robert A. , Maini Philip K. , Anderson Alexander R.A.
Published: April 2024

Standard-of-care treatment regimens have long been designed for maximal cell killing, yet these strategies often fail when applied to metastatic cancers due to the emergence of drug resistance. Adaptive treatment strategies have been developed as an alternative approach, dynamically adjusting treatment to suppress the growth of treatment-resistant populations and thereby delay, or even prevent, tumor progression. Promising clinical results in prostate cancer indicate the potential to optimize adaptive treatment protocols. Here, we applied deep reinforcement learning (DRL) to guide adaptive drug scheduling and demonstrated that these treatment schedules can outperform the current adaptive protocols in a mathematical model calibrated to prostate cancer dynamics, more than doubling the time to progression. The DRL strategies were robust to patient variability, including both tumor dynamics and clinical monitoring schedules. The DRL framework could produce interpretable, adaptive strategies based on a single tumor burden threshold, replicating and informing optimal treatment strategies. The DRL framework had no knowledge of the underlying mathematical tumor model, demonstrating the capability of DRL to help develop treatment strategies in novel or complex settings. Finally, a proposed five-step pathway, which combined mechanistic modeling with the DRL framework and integrated conventional tools to improve interpretability compared with traditional “black-box” DRL models, could allow translation of this approach to the clinic. Overall, the proposed framework generated personalized treatment schedules that consistently outperformed clinical standard-of-care protocols.

Significance:

Generation of interpretable and personalized adaptive treatment schedules using a deep reinforcement framework that interacts with a virtual patient model overcomes the limitations of standardized strategies caused by heterogeneous treatment responses.
Supplementary Materials and Methods from Patterns of Cancer-Related Healthcare Access across Pennsylvania: Analysis of Novel Census Tract-Level Indicators of Persistent Poverty
Authors: Moss Jennifer L. , Geyer Nathaniel R. , Lengerich Eugene J.
Published: April 2024

The data elements assessed in the current study, as well as study code, are available in Supplementary Materials and Methods.
Supplementary Table S7 from Trends and Disparities in Curative-Intent Treatment for Early-Stage Non–Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT
Authors: Liu Qinran , Medina Heidy N. , Rodriguez Estelamari , Jacobs Kamaria T. , Brown Clyde , Koru-Sengul Tulay , Lopes Gilberto , Pinheiro Paulo S.
Published: April 2024

Supplementary Table S7 shows the determinants of receipt of curative-intent surgery and receipt of any curative-intent treatment with adjustment for measures of geographical proximity to major healthcare centers in Florida from 2005 to 2017.
Supplementary Table 4 from The Associations between Intakes of One-Carbon Metabolism–Related Vitamins and Breast Density among Young Women
Authors: Han Eunyoung , Van Horn Linda , Snetselaar Linda , Shepherd John A. , Park Yoon Jung , Kim Hyesook , Jung Seungyoun , Dorgan Joanne F.
Published: April 2024

Supplementary Table 4 shows the results of association between �V and ADBV according to quartiles of one-carbon metabolism-related vitamin intakes during youth and at specific pubertal stages among nulliparous women
Supplementary Table S6 from Trends and Disparities in Curative-Intent Treatment for Early-Stage Non–Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT
Authors: Liu Qinran , Medina Heidy N. , Rodriguez Estelamari , Jacobs Kamaria T. , Brown Clyde , Koru-Sengul Tulay , Lopes Gilberto , Pinheiro Paulo S.
Published: April 2024

Supplementary Table S6 shows the determinants of receipt of curative-intent surgery and receipt of any curative-intent treatment in Hispanic subgroups in Florida from 2005 to 2017.
Supplementary Table 3 from The Associations between Intakes of One-Carbon Metabolism–Related Vitamins and Breast Density among Young Women
Authors: Han Eunyoung , Van Horn Linda , Snetselaar Linda , Shepherd John A. , Park Yoon Jung , Kim Hyesook , Jung Seungyoun , Dorgan Joanne F.
Published: April 2024

Supplementary table 3 shows the results of association between �V and ADBV according to intakes of one-carbon metabolism related vitamins during adulthood stratified by adolsecents' levels of one-carbon metabolism-related vitamins intakes
Supplementary Table S3 from Trends and Disparities in Curative-Intent Treatment for Early-Stage Non–Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT
Authors: Liu Qinran , Medina Heidy N. , Rodriguez Estelamari , Jacobs Kamaria T. , Brown Clyde , Koru-Sengul Tulay , Lopes Gilberto , Pinheiro Paulo S.
Published: April 2024

Supplementary Table S3 shows the determinants of patients who only received SBRT by CCI in Florida from 2005 to 2017.
Supplementary Table S2 from Trends and Disparities in Curative-Intent Treatment for Early-Stage Non–Small Cell Lung Cancer: A Population-Based Analysis of Surgery and SBRT
Authors: Liu Qinran , Medina Heidy N. , Rodriguez Estelamari , Jacobs Kamaria T. , Brown Clyde , Koru-Sengul Tulay , Lopes Gilberto , Pinheiro Paulo S.
Published: April 2024

Supplementary Table S2 shows the full list of characteristics of the study population by curative-intent treatment groups in Florida from 2005 to 2017.
Supplementary Table S1 from Do Contemporary Cancer Survivors Experience Better Quality of Life? Evaluating a Decade of SEER Medicare Health Outcomes Survey Data
Authors: Allaire Benjamin T. , Horvath Marc L. , Lines Lisa M. , Davidoff Amy J. , Smith Ashley Wilder , Jensen Roxanne E.
Published: April 2024

Supplementary Table S1 lists the IC-O-3 site codes for the ten cancers analyzed in the manuscript.
Supplementary Table 4. from Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study
Authors: Yoon Hyung-Suk , Wu Jie , Shidal Chris , Sun Yan , Franke Adrian A. , Yang Jae Jeong , Braithwaite Dejana , Courtney Regina , Cai Hui , Blot William J. , Shu Xiao-Ou , Zheng Wei , Cai Qiuyin
Published: April 2024

Association between Plasma Tocopherols and Lung Cancer Risk by Smoking Pack-Years
Supplementary Table 3. from Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study
Authors: Yoon Hyung-Suk , Wu Jie , Shidal Chris , Sun Yan , Franke Adrian A. , Yang Jae Jeong , Braithwaite Dejana , Courtney Regina , Cai Hui , Blot William J. , Shu Xiao-Ou , Zheng Wei , Cai Qiuyin
Published: April 2024

Association between Plasma Tocopherols and Lung Cancer Risk by Sex
Supplementary Table 2. from Associations between Plasma Tocopherols and Lung Cancer Risk: Results from the Southern Community Cohort Study
Authors: Yoon Hyung-Suk , Wu Jie , Shidal Chris , Sun Yan , Franke Adrian A. , Yang Jae Jeong , Braithwaite Dejana , Courtney Regina , Cai Hui , Blot William J. , Shu Xiao-Ou , Zheng Wei , Cai Qiuyin
Published: April 2024

Association between Plasma Tocopherols and Lung Cancer Risk by Race
Supplemental Figure 4 from Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study
Authors: Duncan Meredith S. , Diaz-Zabala Hector , Jaworski James , Tindle Hilary A. , Greevy Robert A. , Lipworth Loren , Hung Rayjean J. , Freiberg Matthew S. , Aldrich Melinda C.
Published: April 2024

Supplemental Figure 4: Overlaid histograms showing the distribution of polygenic risk scores by case/non-case status
Supplemental Figure 3 from Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study
Authors: Duncan Meredith S. , Diaz-Zabala Hector , Jaworski James , Tindle Hilary A. , Greevy Robert A. , Lipworth Loren , Hung Rayjean J. , Freiberg Matthew S. , Aldrich Melinda C.
Published: April 2024

Supplemental Figure 3: PRS Model fit by p-value threshold. High resolution plots displaying the -log10(p-value) of the association between lung cancer and the PRS in the FHS sample (y-axis) versus the threshold below which all SNPs with p-values for their individual association with lung cancer in the base sample (OncoArray Consortium) were included (x-axis).
Supplemental Table S3 from Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study
Authors: Huang Robert J. , Huang Edward S. , Mudiganti Satish , Chen Tony , Martinez Meghan C. , Ramrakhiani Sanjay , Han Summer S. , Hwang Joo Ha , Palaniappan Latha P. , Liang Su-Ying
Published: April 2024

Supplemental Table S3: Recoding schema for smoking variable structured data element in electronic health record (EHR).
Supplemental Table S1 from Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study
Authors: Huang Robert J. , Huang Edward S. , Mudiganti Satish , Chen Tony , Martinez Meghan C. , Ramrakhiani Sanjay , Han Summer S. , Hwang Joo Ha , Palaniappan Latha P. , Liang Su-Ying
Published: April 2024

Supplemental Table S1: Each count represents the number of unique encounters available for information capture in the cohort between January 1, 2010 and December 31, 2020.
Supplemental Figure S1 from Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study
Authors: Huang Robert J. , Huang Edward S. , Mudiganti Satish , Chen Tony , Martinez Meghan C. , Ramrakhiani Sanjay , Han Summer S. , Hwang Joo Ha , Palaniappan Latha P. , Liang Su-Ying
Published: April 2024

Supplemental Figure S1: Analytic flowchart demonstrating cohort inclusion and exclusion criteria, linkage with Palo Alto Medical Foundation (PAMF) tumor registry, and downstream time-to-event capture. GAC, gastric adenocarcinoma.
Supplementary Table 7 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Table 7 shows the cis-meQTLs residing in same location as PCa-risk SNPs with p < 5x10-8 in the Schumacher et a. GWAS of PCa in AA benign tissue
Supplementary Table 6 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Table 6 shows the replication of 110 autosomal PCa-risk cis-meQTLs (p < 1x10-9) reported in Dai et al. al., 2020
Supplementary Table 4 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Table 4 shows the replication of 7,590 genome-wide tumor cis-meQTLs reported in Houlahan et al., 2019
Supplemental Figure 4 from Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years
Authors: D'Souza Gypsyamber , Tewari Sakshi R. , Troy Tanya , Webster-Cyriaque Jennifer , Wiley Dorothy J. , Lahiri Cecile Delille , Palella Frank Joseph , Gillison Maura L. , Strickler Howard D. , Struijk Linda , Waterboer Tim , Ho Ken , Kwait Jennafer , Lazar Jason , Weber Kathleen M. , Fakhry Carole
Published: April 2024

Supplemental Figure 4: Effect of sex on prevalent (SF4a) incident (SF4b) infections.
Supplemental Figure 2 from Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years
Authors: D'Souza Gypsyamber , Tewari Sakshi R. , Troy Tanya , Webster-Cyriaque Jennifer , Wiley Dorothy J. , Lahiri Cecile Delille , Palella Frank Joseph , Gillison Maura L. , Strickler Howard D. , Struijk Linda , Waterboer Tim , Ho Ken , Kwait Jennafer , Lazar Jason , Weber Kathleen M. , Fakhry Carole
Published: April 2024

Supplemental Figure 2: Clearance of prevalent (panel A) and incident (panel B) oral HPV16 infections over 10 years
Supplemental Figure 1 from Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years
Authors: D'Souza Gypsyamber , Tewari Sakshi R. , Troy Tanya , Webster-Cyriaque Jennifer , Wiley Dorothy J. , Lahiri Cecile Delille , Palella Frank Joseph , Gillison Maura L. , Strickler Howard D. , Struijk Linda , Waterboer Tim , Ho Ken , Kwait Jennafer , Lazar Jason , Weber Kathleen M. , Fakhry Carole
Published: April 2024

Supplemental Figure 1: Flowchart of the 1833 MACS and WIHS participants in the POPS, how many had oncogenic oral HPV DNA, and how many had additional follow-up of uncleared infections as part of the MOUTH study.
Supplementary Table 15 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Table 15 shows the posterior probabilities that GWAS and tumor-meQTLs share the same causal variant.
Supplementary Table 13 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Table 13 shows the cis-meQTLs residing in same location as PCa-risk SNPs with p < 5x10-8 in the Schumacher et al. GWAS of PCa in EA tumor tissue
Supplementary Table 2 from Racial and Ethnic Disparities in Hepatocellular Carcinoma Treatment Receipt in the United States: A Systematic Review and Meta-Analysis
Authors: Wagle Nikita Sandeep , Park Sulki , Washburn David , Ohsfeldt Robert , Kum Hye-Chung , Singal Amit G.
Published: April 2024

SES and geographic covariates included in the multivariable analysis of receipt of HCC treatment.
Supplementary Table 1 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Table 1 shows the priors for co-localization analysis
Supplementary Figure 1 from Racial and Ethnic Disparities in Hepatocellular Carcinoma Treatment Receipt in the United States: A Systematic Review and Meta-Analysis
Authors: Wagle Nikita Sandeep , Park Sulki , Washburn David , Ohsfeldt Robert , Kum Hye-Chung , Singal Amit G.
Published: April 2024

Supplementary figure 1 shows that of the 10356 records identified through the electronic databases, 15 studies were included in the meta-analyses.
Citation: Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71
Supplementary Figure 5 from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

Supplementary Figure 5 shows the comparison of beta coefficients for cis-meQTLs by ancestry and tissue type
Supplementary Table 7 from Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes
Authors: Zeldin Jordan , Sandler Dale P. , Ogunsina Kemi , O'Brien Katie M.
Published: April 2024

Association between endometriosis and triple negative subtype among cases stratified by race/ethnicity, using logistic regression models
Supplementary Table 1 from Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes
Authors: Zeldin Jordan , Sandler Dale P. , Ogunsina Kemi , O'Brien Katie M.
Published: April 2024

Association between fibroids diagnosed before age 35 (+/- uterine surgery) and breast cancer incidence, stratified by menopause status, using Cox proportional hazards models
Data from The Reach of Calls and Text Messages for Mailed FIT Outreach in the PROMPT Stepped-Wedge Colorectal Cancer Screening Trial
Authors: Coronado Gloria D. , Nyongesa Denis B. , Petrik Amanda F. , Thompson Jamie H. , Escaron Anne L. , Pham Tuan , Leo Michael C.
Published: April 2024

AbstractBackground:
Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer screening participation. We assessed the reach and effectiveness of adding notifications to mailed FIT programs.
Methods:
We conducted secondary analyses of a stepped-wedge evaluation of an enhanced mailed FIT program (n = 15 clinics). Patients were stratified by prior FIT completion. Those with prior FIT were sent a text message (Group 1); those without were randomized 1:1 to receive a text message (Group 2) or live phone call (Group 3). All groups were sent automated phone call reminders. In stratified analysis, we measured reach and effectiveness (FIT completion within 6 months) and assessed patient-level associations using generalized estimating equations.
Results:
Patients (n = 16,934; 83% Latino; 72% completed prior FIT) were reached most often by text messages (78%), followed by live phone calls (71%), then automated phone calls (56%). FIT completion was higher in patients with prior FIT completion versus without [44% (Group 1) vs. 19% (Group 2 + Group 3); P < 0.01]. For patients without prior FIT, effectiveness was higher in those allocated to a live phone call [20% (Group 3) vs. 18% (Group 2) for text message; P = 0.04] and in those who personally answered the live call (28% vs. 9% no call completed; P < 0.01).
Conclusions:
Text messages reached the most patients, yet effectiveness was highest in those who personally answered the live phone call.
Impact:
Despite the broad reach and low cost of text messages, personalized approaches may more successfully boost FIT completion.
Data from The Associations between Intakes of One-Carbon Metabolism–Related Vitamins and Breast Density among Young Women
Authors: Han Eunyoung , Van Horn Linda , Snetselaar Linda , Shepherd John A. , Park Yoon Jung , Kim Hyesook , Jung Seungyoun , Dorgan Joanne F.
Published: April 2024

AbstractBackground:
Folate is the primary methyl donor and B vitamins are cofactors for one-carbon metabolism that maintain DNA integrity and epigenetic signatures implicated in carcinogenesis. Breast tissue is particularly susceptible to stimuli in early life. Only limited data are available on associations of one-carbon metabolism–related vitamin intake during youth and young adulthood with breast density, a strong risk factor for breast cancer.
Methods:
Over 18 years in the DISC and DISC06 Follow-up Study, diets of 182 young women were assessed by three 24-hour recalls on five occasions at ages 8 to 18 years and once at 25 to 29 years. Multivariable-adjusted linear mixed-effects regression was used to examine associations of intakes of one-carbon metabolism-related vitamins with MRI-measured percent dense breast volume (�V) and absolute dense breast volume (ADBV) at ages 25 to 29 years.
Results:
Folate intake in youth was inversely associated with �V (Ptrend = 0.006) and ADBV (Ptrend = 0.02). These inverse associations were observed with intake during post-, though not premenarche. In contrast, premenarche vitamin B2 intake was positively associated with ADBV (Ptrend < 0.001). Young adult folate and vitamin B6 intakes were inversely associated with �V (all Ptrend ≤ 0.04), whereas vitamins B6 and B12 were inversely associated with ADBV (all Ptrend ≤ 0.04).
Conclusions:
Among these DISC participants intakes of one-carbon metabolism-related vitamins were associated with breast density. Larger prospective studies among diverse populations are needed to replicate these findings.
Impact:
Our results suggest the importance of one-carbon metabolism-related vitamin intakes early in life with development of breast density and thereby potentially breast cancer risk later in life.
Data from Risk Factors for Ovarian Cancer by BRCA Status: A Collaborative Case-Only Analysis
Authors: Gersekowski Kate , Na Renhua , Alsop Kathryn , Delahunty Rachel , Goode Ellen L. , Cunningham Julie M. , Winham Stacey J. , Pharoah Paul D.P. , Song Honglin , Webb Penelope M.
Published: April 2024

AbstractBackground:
Women with an inherited pathogenic variant in BRCA1 or BRCA2 have a greatly increased risk of developing ovarian cancer, but the importance of behavioral factors is less clear. We used a case-only design to compare the magnitude of associations with established reproductive, hormonal, and lifestyle risk factors between BRCA mutation carriers and noncarriers.
Methods:
We pooled data from five studies from the Ovarian Cancer Association Consortium including 637 BRCA carriers and 4,289 noncarriers. Covariate-adjusted generalized linear mixed models were used to estimate interaction risk ratios (IRR) and 95% confidence intervals (CI), with BRCA (carrier vs. noncarrier) as the response variable.
Results:
IRRs were above 1.0 for known protective factors including ever being pregnant (IRR = 1.29, 95% CI; 1.00–1.67) and ever using the oral contraceptive pill (1.30, 95% CI; 1.07–1.60), suggesting the protective effects of these factors may be reduced in carriers compared with noncarriers. Conversely, the IRRs for risk factors including endometriosis and menopausal hormone therapy were below 1.0, suggesting weaker positive associations among BRCA carriers. In contrast, associations with lifestyle factors including smoking, physical inactivity, body mass index, and aspirin use did not appear to differ by BRCA status.
Conclusions:
Our results suggest that associations with hormonal and reproductive factors are generally weaker for those with a pathogenic BRCA variant than those without, while associations with modifiable lifestyle factors are similar for carriers and noncarriers.
Impact:
Advice to maintain a healthy weight, be physically active, and refrain from smoking will therefore benefit BRCA carriers as well as noncarriers.
Data from Sleep and Risk of Pancreatic Cancer in the UK Biobank
Authors: Freeman Joshua R. , Saint-Maurice Pedro F. , Zhang Ting , Matthews Charles E. , Stolzenberg-Solomon Rachael Z.
Published: April 2024

AbstractBackground:
Light at night, which may cause circadian disruption, is a potential pancreatic cancer risk factor. However, evidence from related exposures such as poor sleep health and shift work remains inconclusive and sparsely investigated.
Methods:
We evaluated associations between self-reported typical sleep duration, chronotype, shift work, insomnia symptoms, snoring, and daytime sleeping and pancreatic ductal adenocarcinomas (PDAC) incidence among 475,286 UK Biobank participants. We used Cox proportional hazards models to estimate HRs and 95% confidence intervals (CI) adjusting for age, sex, body mass index, smoking status, duration, and frequency, alcohol intake, diabetes status, race, and employment/shift work.
Results:
Over 14 years of follow-up, 1,079 adults were diagnosed with PDAC. There were no associations observed between sleep characteristics, including sleep duration [<7 vs. 7–<9 hours; HR, 1.03; 95% CI, 0.90–1.19; ≥9 hours; HR, 1.00 (0.81–1.24), evening chronotype (“definitely” an evening person vs. “definitely” a morning person; HR, 0.99 (0.77–1.29)], shift work, insomnia symptoms, snoring, or daytime sleep and PDAC risk.
Conclusions:
Self-reported typical sleep characteristics and shift work were not associated with PDAC risk.
Impact:
Considering the role of light at night and shift work in circadian disruption and cancer risk, it is plausible that poor sleep health among a general population may be related to cancer risk through similar sleep and circadian disrupting processes. This work may suggest that typical sleep characteristics and shift work are not associated with PDAC, although additional work is needed to confirm these findings.
Data from Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study
Authors: Huang Robert J. , Huang Edward S. , Mudiganti Satish , Chen Tony , Martinez Meghan C. , Ramrakhiani Sanjay , Han Summer S. , Hwang Joo Ha , Palaniappan Latha P. , Liang Su-Ying
Published: April 2024

AbstractBackground:
Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care.
Methods:
This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40–75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods.
Results:
The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6–3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7–3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1–3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2–9.3), and anemia (HR: 1.9, 95% CI: 1.3–2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2–0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC.
Conclusions:
Routine EHR data can stratify the general population for GAC risk.
Impact:
Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.
Data from Interaction between Continuous Pack-Years Smoked and Polygenic Risk Score on Lung Cancer Risk: Prospective Results from the Framingham Heart Study
Authors: Duncan Meredith S. , Diaz-Zabala Hector , Jaworski James , Tindle Hilary A. , Greevy Robert A. , Lipworth Loren , Hung Rayjean J. , Freiberg Matthew S. , Aldrich Melinda C.
Published: April 2024

AbstractBackground:
Lung cancer risk attributable to smoking is dose dependent, yet few studies examining a polygenic risk score (PRS) by smoking interaction have included comprehensive lifetime pack-years smoked.
Methods:
We analyzed data from participants of European ancestry in the Framingham Heart Study Original (n = 454) and Offspring (n = 2,470) cohorts enrolled in 1954 and 1971, respectively, and followed through 2018. We built a PRS for lung cancer using participant genotyping data and genome-wide association study summary statistics from a recent study in the OncoArray Consortium. We used Cox proportional hazards regression models to assess risk and the interaction between pack-years smoked and genetic risk for lung cancer adjusting for European ancestry, age, sex, and education.
Results:
We observed a significant submultiplicative interaction between pack-years and PRS on lung cancer risk (P = 0.09). Thus, the relative risk associated with each additional 10 pack-years smoked decreased with increasing genetic risk (HR = 1.56 at one SD below mean PRS, HR = 1.48 at mean PRS, and HR = 1.40 at one SD above mean PRS). Similarly, lung cancer risk per SD increase in the PRS was highest among those who had never smoked (HR = 1.55) and decreased with heavier smoking (HR = 1.32 at 30 pack-years).
Conclusions:
These results suggest the presence of a submultiplicative interaction between pack-years and genetics on lung cancer risk, consistent with recent findings. Both smoking and genetics were significantly associated with lung cancer risk.
Impact:
These results underscore the contributions of genetics and smoking on lung cancer risk and highlight the negative impact of continued smoking regardless of genetic risk.
Data from The Impact of Inherited Genetic Variation on DNA Methylation in Prostate Cancer and Benign Tissues of African American and European American Men
Authors: Delgado Dayana , Gillard Marc , Tong Lin , Demanelis Kathryn , Oliva Meritxell , Gleason Kevin J. , Chernoff Meytal , Chen Lin , Paner Gladell P. , Vander Griend Donald , Pierce Brandon L.
Published: April 2024

AbstractBackground:
American men of African ancestry (AA) have higher prostate cancer incidence and mortality rates compared with American men of European ancestry (EA). Differences in genetic susceptibility mechanisms may contribute to this disparity.
Methods:
To gain insights into the regulatory mechanisms of prostate cancer susceptibility variants, we tested the association between SNPs and DNA methylation (DNAm) at nearby CpG sites across the genome in benign and cancer prostate tissue from 74 AA and 74 EA men. Genome-wide SNP data (from benign tissue) and DNAm were generated using Illumina arrays.
Results:
Among AA men, we identified 6,298 and 2,641 cis-methylation QTLs (meQTL; FDR of 0.05) in benign and tumor tissue, respectively, with 6,960 and 1,700 detected in EA men. We leveraged genome-wide association study (GWAS) summary statistics to identify previously reported prostate cancer GWAS signals likely to share a common causal variant with a detected meQTL. We identified nine GWAS-meQTL pairs with strong evidence of colocalization (four in EA benign, three in EA tumor, two in AA benign, and three in AA tumor). Among these colocalized GWAS-meQTL pairs, we identified colocalizing expression quantitative trait loci (eQTL) impacting four eGenes with known roles in tumorigenesis.
Conclusions:
These findings highlight epigenetic regulatory mechanisms by which prostate cancer-risk SNPs can modify local DNAm and/or gene expression in prostate tissue.
Impact:
Overall, our findings showed general consistency in the meQTL landscape of AA and EA men, but meQTLs often differ by tissue type (normal vs. cancer). Ancestry-based linkage disequilibrium differences and lack of AA representation in GWAS decrease statistical power to detect colocalization for some regions.
Data from Oncogenic Oral Human Papillomavirus Clearance Patterns over 10 Years
Authors: D'Souza Gypsyamber , Tewari Sakshi R. , Troy Tanya , Webster-Cyriaque Jennifer , Wiley Dorothy J. , Lahiri Cecile Delille , Palella Frank Joseph , Gillison Maura L. , Strickler Howard D. , Struijk Linda , Waterboer Tim , Ho Ken , Kwait Jennafer , Lazar Jason , Weber Kathleen M. , Fakhry Carole
Published: April 2024

AbstractBackground:
Effective screening for oropharyngeal cancer is lacking. Four oncogenic HPV clearance definitions were explored to understand long-term natural history for persistent oncogenic oral HPV (oncHPV), the precursor of oropharyngeal cancer.
Methods:
Prospective multicenter cohort of participants living with/at-risk for HIV, with oral rinse and gargle samples collected every 6 to 12 months for up to 10 years and tested for oncHPV. HPV clearance definitions included 1 (clear1), 2 (clear2), 3 (clear3) consecutive negatives, or being negative at last two visits (clearlast).
Results:
Median time to clearance of oncHPV exceeded 2 years for conservative definitions (clear3: 2.38, clearlast: 2.43), but not lenient (clear1: 0.68, clear2: 1.15). By clear3, most incident infections cleared at 2, 5, 8 years (55.1%, 75.6%, 79.1%), contrary to prevalent infections (37.1%, 52.5%, 59.5%, respectively). In adjusted analysis, prevalent oncHPV, older age, male sex, and living with HIV were associated with reduced clearance. Of 1,833 subjects screened, 13.8% had prevalent oncHPV and 47.5% of those infections persisted ≥5 years, representing 6.5% of persons screened. Two men with prevalent oral HPV16 developed incident oropharyngeal cancer [IR = 1.62 per 100 person-years; 95% confidence interval (CI), 0.41–6.4]. Many with oral HPV16 persisted ≥5 years (and/or developed HPV-oropharyngeal cancer) among those with 2 (72.2%), ≥2 of first 3 (65.7%), or 3 (80.0%) consecutive positive oHPV16 tests, but not after 1 (39.4%).
Conclusions:
In our 10-year study, most incident infections cleared quickly. However, half of prevalent oncHPV persisted ≥5 years, suggesting increased risk with persistent oncHPV at >2 visits.
Impact:
We identified groups with persistent oncHPV at increased risk of oropharyngeal cancer and contextualized risk levels for those with oral HPV16 infection.
Data from Association of Fibroids, Endometriosis, and Gynecologic Surgeries with Breast Cancer Incidence and Hormone Receptor Subtypes
Authors: Zeldin Jordan , Sandler Dale P. , Ogunsina Kemi , O'Brien Katie M.
Published: April 2024

AbstractBackground:
Fibroids and endometriosis are sex hormone–mediated and exhibit cancer-like behavior. Breast cancer may be more common in women who have had these conditions, but the literature is conflicting and does not always address factors like hysterectomy/oophorectomy status, race/ethnicity, menopause, and hormone receptor subtypes.
Methods:
Data are from the Sister Study, a cohort of 50,884 U.S. women enrolled in 2003 to 2009 and followed through 2020. Cox proportional hazards models with time-varying exposures and covariates assessed the relationship of fibroids or endometriosis with breast cancer. Logistic regression examined the association with estrogen receptor (ER) status among cases.
Results:
Fibroids (19,932 cases) were positively associated with breast cancer [fully adjusted HR: 1.07; 95% confidence interval (CI): 1.01–1.14], notably among Black participants (HR: 1.34; 95% CI: 1.07–1.69) and women who had a hysterectomy (HR: 1.18; 95% CI: 1.05–1.31). Endometriosis (3,970 cases) was not associated with breast cancer (HR: 0.99; 95% CI: 0.91–1.08). Among 4,419 breast cancer cases, fibroids were positively associated with ER+ subtypes (OR: 1.34; 95% CI: 1.10–1.65), while endometriosis was negatively associated with ER+ subtypes (OR: 0.78; 95% CI: 0.61–1.01).
Conclusions:
We observed a modest positive association between fibroids and breast cancer, particularly ER+ breast cancer. No relationship with endometriosis and breast cancer incidence was found.
Impact:
Fibroids, even in those with a family history of breast cancer, might modify breast cancer risk stratification tools. Future studies should further assess this link and interrogate shared risk factors.
Supplementary Table 3 from Genomic Complexity Predicts Resistance to Endocrine Therapy and CDK4/6 Inhibition in Hormone Receptor–Positive (HR+)/HER2-Negative Metastatic Breast Cancer
Authors: Davis Andrew A. , Luo Jingqin , Zheng Tiantian , Dai Chao , Dong Xiaoxi , Tan Lu , Suresh Rama , Ademuyiwa Foluso O. , Rigden Caron , Rearden Timothy P. , Clifton Katherine , Weilbaecher Katherine , Frith Ashley , Tandra Pavan K. , Summa Tracy , Haas Brittney , Thomas Shana , Hernandez-Aya Leonel F. , Peterson Lindsay L. , Wang Xiaohong , Luo Shujun J. , Zhou Kemin , Du Pan , Jia Shidong , King Bonnie L. , Krishnamurthy Jairam , Ma Cynthia X.
Published: April 2024

Gene alterations associated with shorter PFS.
Figure S5 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases
Authors: Von Roemeling Christina A. , Doonan Bently P. , Klippel Kelena , Schultz Daniel , Hoang-Minh Lan , Trivedi Vrunda , Li Chenglong , Russell Rylynn A. , Kanumuri Raju S. , Sharma Abhisheak , Tun Han W. , Mitchell Duane A.
Published: April 2024

Supplemental Figure 5: Chromatogram of CA-4948.
Supplementary Methods S1 from Genomic Complexity Predicts Resistance to Endocrine Therapy and CDK4/6 Inhibition in Hormone Receptor–Positive (HR+)/HER2-Negative Metastatic Breast Cancer
Authors: Davis Andrew A. , Luo Jingqin , Zheng Tiantian , Dai Chao , Dong Xiaoxi , Tan Lu , Suresh Rama , Ademuyiwa Foluso O. , Rigden Caron , Rearden Timothy P. , Clifton Katherine , Weilbaecher Katherine , Frith Ashley , Tandra Pavan K. , Summa Tracy , Haas Brittney , Thomas Shana , Hernandez-Aya Leonel F. , Peterson Lindsay L. , Wang Xiaohong , Luo Shujun J. , Zhou Kemin , Du Pan , Jia Shidong , King Bonnie L. , Krishnamurthy Jairam , Ma Cynthia X.
Published: April 2024

Supplementary Methods
Figure S1 from Oral IRAK-4 Inhibitor CA-4948 Is Blood-Brain Barrier Penetrant and Has Single-Agent Activity against CNS Lymphoma and Melanoma Brain Metastases
Authors: Von Roemeling Christina A. , Doonan Bently P. , Klippel Kelena , Schultz Daniel , Hoang-Minh Lan , Trivedi Vrunda , Li Chenglong , Russell Rylynn A. , Kanumuri Raju S. , Sharma Abhisheak , Tun Han W. , Mitchell Duane A.
Published: April 2024

Supplemental Figure 1. Myddosome signaling in normal human cerebral cortex.
Supplementary Table S1 from Impact of Biomarker-Matched Therapies on Outcomes in Patients with Sarcoma Enrolled in Early-Phase Clinical Trials (SAMBA 101)
Authors: Carmagnani Pestana Roberto , Moyers Justin T. , Roszik Jason , Sen Shiraj , Hong David S. , Naing Aung , Herzog Cynthia E. , Fu Siqing , Piha-Paul Sarina A. , Rodon Jordi , Yap Timothy A. , Karp Daniel D. , Tsimberidou Apostolia M. , Pant Shubham , Zarzour Maria A. , Ratan Ravin , Ravi Vinod , Benjamin Robert S. , Lazar Alexander J. , Wang Wei-Lien , Daw Najat , Gill Jonathan B. , Harrison Douglas J. , Lewis Valerae O. , Roland Christina L. , Patel Shreyaskumar R. , Livingston J. Andrew , Somaiah Neeta , Ludwig Joseph A. , Conley Anthony P. , Hamerschlak Nelson , Gorlick Richard , Meric-Bernstam Funda , Subbiah Vivek
Published: April 2024

Summary of response outcomes across subgroups
Supplementary Figure S2 from Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riyue , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J.
Published: April 2024

MUC1 expression and immune infiltrate in baseline and recurrent adenoma pairs
Supplementary Figure S1 from Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riyue , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J.
Published: April 2024

Endpoint titers of plasma antibodies at week 12 amongst vaccine responders
Supplementary Data S3 from BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma
Authors: Kurata Keiji , Samur Mehmet K. , Liow Priscilla , Wen Kenneth , Yamamoto Leona , Liu Jiye , Morelli Eugenio , Gulla Annamaria , Tai Yu-Tzu , Qi Jun , Hideshima Teru , Anderson Kenneth C.
Published: April 2024

GSEA_RNAseq (GOBP)
Supplementary Figure S6 from NPY Methylated ctDNA is a Promising Biomarker for Treatment Response Monitoring in Metastatic Colorectal Cancer
Authors: Janssens Katleen , Vanhoutte Greetje , Lybaert Willem , Demey Wim , Decaestecker Jochen , Hendrickx Koen , Rezaei Kalantari Hassan , Zwaenepoel Karen , Pauwels Patrick , Fransen Erik , Op de Beeck Ken , Van Camp Guy , Rolfo Christian , Peeters Marc
Published: April 2024

Follow-up of patients during treatment using methylated ctDNA.
Supplementary Figures S1-11 from CEACAM1 Marks Highly Suppressive Intratumoral Regulatory T Cells for Targeted Depletion Therapy
Authors: Jeon Seung Hyuck , Kang Minyong , Jeon Minwoo , Chung Youseung , Kim A Reum , Lee Yong Joon , Kim Eui-Soon , Nam Heejin , Park Junsik , Lee Jung-Yun , Shin Eui-Cheol , Seo Seong Il , Park Su-Hyung
Published: April 2024

Supplementary Figures S1-11
Supplementary Figure S2 from NPY Methylated ctDNA is a Promising Biomarker for Treatment Response Monitoring in Metastatic Colorectal Cancer
Authors: Janssens Katleen , Vanhoutte Greetje , Lybaert Willem , Demey Wim , Decaestecker Jochen , Hendrickx Koen , Rezaei Kalantari Hassan , Zwaenepoel Karen , Pauwels Patrick , Fransen Erik , Op de Beeck Ken , Van Camp Guy , Rolfo Christian , Peeters Marc
Published: April 2024

Kaplan Meier curve for progression free survival.
Supplementary Figures S1-S17 from Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance
Authors: Carney Stephen V. , Banerjee Kaushik , Mujeeb Anzar , Zhu Brandon , Haase Santiago , Varela Maria L. , Kadiyala Padma , Tronrud Claire E. , Zhu Ziwen , Mukherji Devarshi , Gorla Preethi , Sun Yilun , Tagett Rebecca , Núñez Felipe J. , Luo Maowu , Luo Weibo , Ljungman Mats , Liu Yayuan , Xia Ziyun , Schwendeman Anna , Qin Tingting , Sartor Maureen A. , Costello Joseph F. , Cahill Daniel P. , Lowenstein Pedro R. , Castro Maria G.
Published: April 2024

Supplementary Figures and Figure Legends
FIGURE 6 from Versican Associates with Tumor Immune Phenotype and Limits T-cell Trafficking via Chondroitin Sulfate
Authors: Hirani Priyanka , McDermott Jacqueline , Rajeeve Vinothini , Cutillas Pedro R. , Jones J. Louise , Pennington Daniel J. , Wight Thomas N. , Santamaria Salvatore , Alonge Kimberly M. , Pearce Oliver M.T.
Published: April 2024

CS isomers expression in tissues. A, Structure of CS isoforms following digestion of the chains with ChABC. CS extracted from FFPE tissues in the epithelial zone and stromal zone. CS isoforms analyzed by MS to identify proportion of each isomer. B, Comparison of isoforms in excluded and inflamed tissues within the different zones. Two-way ANOVA. C, Comparison of isomer in the different zones within excluded and inflamed tissues. Two-way ANOVA. D, CS-A/C ratio determined for the different regions of each phenotype and compared. ANOVA. E, Level of sulfation per CS disaccharide in the different regions of each phenotype compared. *, P < 0.05; **, P < 0.01; ****, P < 0.001.
Data from Versican Associates with Tumor Immune Phenotype and Limits T-cell Trafficking via Chondroitin Sulfate
Authors: Hirani Priyanka , McDermott Jacqueline , Rajeeve Vinothini , Cutillas Pedro R. , Jones J. Louise , Pennington Daniel J. , Wight Thomas N. , Santamaria Salvatore , Alonge Kimberly M. , Pearce Oliver M.T.
Published: April 2024

Abstract
Immunotherapies for cancers of epithelial origin have limited efficacy, and a growing body of evidence links the composition of extracellular matrix (ECM) with the likelihood of a favorable response to treatment. The ECM may be considered an immunologic barrier, restricting the localization of cytotoxic immune cells to stromal areas and inhibiting their contact with tumor cells. Identifying ECM components of this immunologic barrier could provide targets that whether degraded in situ may support antitumor immunity and improve immunotherapy response. Using a library of primary triple-negative breast cancer tissues, we correlated CD8+ T-cell tumor contact with ECM composition and identified a proteoglycan, versican (VCAN), as a putative member of the immunologic barrier. Our analysis reveals that CD8+ T-cell contact with tumor associates with the location of VCAN expression, the specific glycovariant of VCAN [defined through the pattern of posttranslational attachments of glycosaminoglycans (GAG)], and the cell types that produce the variant. In functional studies, the isomers of chondroitin sulfate presented on VCAN have opposing roles being either supportive or inhibiting of T-cell trafficking, and removal of the GAGs ameliorates these effects on T-cell trafficking. Overall, we conclude that VCAN can either support or inhibit T-cell trafficking within the tumor microenvironment depending on the pattern of GAGs present, and that VCAN is a major component of the ECM immunologic barrier that defines the type of response to immunotherapy.
Significance:
The response to immunotherapy has been poor toward solid tumors despite immune cells infiltrating into the tumor. The ECM has been associated with impacting T-cell infiltration toward the tumor and in this article we have identified VCAN and its structural modification, chondroitin sulfate as having a key role in T-cell invasion.