bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer learning graph representations of molecules for pKa, 13C-NMR, and solubility
Authors: El-Samman A.M. , De Castro S. , Morton B. , De Baerdemacker S.
Published: February 2024

We explore transfer learning models from a pre-trained graph convolutional neural network representation of molecules, obtained from SchNet, to predict 13C-NMR, pKa, and log  S solubility. SchNet learns a graph representation of a molecule by associating each atom with an “embedding vector” and interacts the atom-embeddings with each other by leveraging graph convolutional filters on their interatomic distances. We pre-trained SchNet on molecular energy and demonstrate that the pre-trained atomistic embeddings can then be used as a transferable representation for a wide array of properties. On the one hand, for atomic properties such as micro-pK1 and 13C-NMR, we investigate two models, one linear and one neural net, that input pre-trained atom-embeddings of a particular atom (e.g. carbon) and predict a local property (e.g., 13C-NMR). On the other hand, for molecular properties such as solubility, a size-extensive graph model is built using the embeddings of all atoms in the molecule as input. For all cases, qualitatively correct predictions are made with relatively little training data (<1000 training points), showcasing the ease with which pre-trained embeddings pick up on important chemical patterns. The proposed models successfully capture well-understood trends of pK1 and solubility. This study advances our understanding of current neural net graph representations and their capacity for transfer learning applications in chemistry.
Climate warming and projected loss of thermal habitat volume in lake populations of brook trout
Authors: Ridgway Mark S. , Smith Darren A. , Bell Allan H.
Published: February 2024

We applied an ensemble of climate warming models to an iconic protected landscape (Algonquin Park, Ontario) and the seasonal temperature profile model for lakes to assess changes in brook trout ( Salvelinus fontinalis) thermal habitat volume (THV) among lakes of different sizes in 30-year periods under two climate warming scenarios (RCP 4.5 and 8.5). Bayesian beta regression models show that lake size (surface area) and morphometry (dynamic lake ratio) are important factors in THV loss. THV loss increases as a function of the dynamic lake ratio (transition from bowl-shaped to dish-shaped lakes). The magnitude of this effect depends on the lake size category and the RCP scenario. Small (<100 ha) and medium (100–500 ha) dish-shaped lakes are projected to have greater THV loss in 2071–2100 (60%–100% of brook trout THV under RCP 8.5; 40%–70% under RCP 4.5) than large lakes (>500 ha) of similar shape. Climate warming projections for the balance of this century, regardless of the RCP category, will result in the loss of brook trout THV in lakes that range widely in size and morphometry.
A Girl with PRRT2 Mutation Presenting with Benign Familial Infantile Seizures Followed by Autistic Regression
Authors: Zhang Li , Wan Zhen-Xia , Zhu Jin-Yi , Liu Hui-Juan , Sun Jin , Zou Xiao-Hui , Zhang Ting , Li Yan
Published: February 2024

Benign familial infantile seizure (BFIS) is an autosomal dominant infantile‐onset epilepsy syndrome with a typically benign prognosis. It is commonly associated with heterozygous mutations of the PRRT2 gene located on chromosome 16p11.2. The frameshift heterozygous mutation (c.649dupC, p.Arg217Profs∗8) in PRRT2 is responsible for the majority of BFIS cases. In this report, we present a rare case of a girl with a confirmed clinical and genetic diagnosis of BFIS due to a frameshift heterozygous mutation in PRRT2 (c.649dupC). She exhibited typical neurodevelopment until 15 months of age, followed by an unexpected severe autistic regression. In addition to BFIS, PRRT2 mutations are also associated with paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions and paroxysmal choreoathetosis (ICCA), indicating a complex genotype‐phenotype heterogeneity in PRRT2 mutations. This clinical observation highlights the possibility that BFIS patients with PRRT2 mutations may not always have a benign neurodevelopmental prognosis, emphasizing the need for long‐term clinical follow‐up.
Patient Satisfaction with the Implementation of Telehealth in Ambulatory Care during the COVID-19 Pandemic: A Single Institution Experience
Authors: Hailu Berhane Yohannes , Berhe Ephrem , Yemane Awol , Atsbha Abera Merhawit , Berhane Samuel , Berhe Fikaden , Belay Saba Abraham , Gebreegziabher Hailu Abraha , Berhe Abreha Bereket , Gebrearegay Haileeyesus Hailemariam , Gidey Kidu
Published: February 2024

Background. COVID-19 has reduced the capacity for delivering essential health services due to lockdown restrictions. Telehealth is an effective alternative option to improve healthcare access. However, there remain implementation challenges to patient adoption in resource-limited settings such as Ethiopia. Therefore, the purpose of this study was to assess patient satisfaction following the implementation of telehealth in ambulatory settings during the COVID-19 pandemic. Methods. A cross-sectional study was conducted at Ayder Comprehensive Specialized Hospital in the Tigray region of Northern Ethiopia. Patients who used the telehealth service were invited to participate in a patient satisfaction survey. All statistical analyses were performed using STATA Version 14.1. Result. A total of 149 patients have participated in the survey. Out of the total participants, 129 (86.6%) found that telehealth is easy to understand and overall satisfaction for telehealth was 87.9%. About two-thirds of the patients (97, 65.1%) reported that the telehealth visit is just as good as a traditional visit. The vast majority of participants (148, 98.6%) stated that they would definitely or probably use telehealth again and would recommend it to others. The majority of respondents (137, 91.9%) followed the recommendations provided. Conclusion. Patients have a high level of satisfaction with the use of telehealth during the COVID-19 pandemic. About two-thirds of patients said the telehealth visit was just as good as a traditional visit. The majority of patients followed the recommendations given to them by the healthcare providers and stated that they would definitely or probably use telehealth in the future and would recommend it to others. This high level of patient satisfaction with telehealth implementation suggests that the service could be considered in low-income countries as well.
Supplementary Table S2 from Clinical Benefit of Avapritinib in KIT-Mutant Gastrointestinal Stromal Tumors: A Post Hoc Analysis of the Phase I NAVIGATOR and Phase I/II CS3007–001 Studies
Authors: Heinrich Michael C. , Zhang Xinhua , Jones Robin L. , George Suzanne , Serrano César , Deng Yanhong , Bauer Sebastian , Cai Shirong , Wu Xin , Zhou Yongjian , Tao Kaixiong , Zheng Zhichao , Zhang Jun , Cui Yuehong , Cao Hui , Wang Meining , Hu Jin , Yang Jason , Li Jian , Shen Lin
Published: February 2024

Supplementary Table S2. Representativeness of the study participants with KIT-mutant gastrointestinal stromal tumors.
Supplementary Tables 1-6 from PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti–PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients
Authors: Denize Thomas , Jegede Opeyemi A. , Matar Sayed , El Ahmar Nourhan , West Destiny J. , Walton Emily , Bagheri Aseman Sheshdeh , Savla Varunika , Nabil Laimon Yasmin , Gupta Saurabh , Vemula Sai Vikram , Braun David A. , Burke Kelly P. , Catalano Paul J. , Freeman Gordon J. , Motzer Robert J. , Atkins Michael B. , McDermott David F. , Sharpe Arlene H. , Choueiri Toni K. , Signoretti Sabina
Published: February 2024

Supplementary Tables 1-6
Figure S4 from PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti–PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients
Authors: Denize Thomas , Jegede Opeyemi A. , Matar Sayed , El Ahmar Nourhan , West Destiny J. , Walton Emily , Bagheri Aseman Sheshdeh , Savla Varunika , Nabil Laimon Yasmin , Gupta Saurabh , Vemula Sai Vikram , Braun David A. , Burke Kelly P. , Catalano Paul J. , Freeman Gordon J. , Motzer Robert J. , Atkins Michael B. , McDermott David F. , Sharpe Arlene H. , Choueiri Toni K. , Signoretti Sabina
Published: February 2024

Figure S4
Figure S2 from PD-1 Expression on Intratumoral Regulatory T Cells Is Associated with Lack of Benefit from Anti–PD-1 Therapy in Metastatic Clear-Cell Renal Cell Carcinoma Patients
Authors: Denize Thomas , Jegede Opeyemi A. , Matar Sayed , El Ahmar Nourhan , West Destiny J. , Walton Emily , Bagheri Aseman Sheshdeh , Savla Varunika , Nabil Laimon Yasmin , Gupta Saurabh , Vemula Sai Vikram , Braun David A. , Burke Kelly P. , Catalano Paul J. , Freeman Gordon J. , Motzer Robert J. , Atkins Michael B. , McDermott David F. , Sharpe Arlene H. , Choueiri Toni K. , Signoretti Sabina
Published: February 2024

Figure S2
Supplementary Data 1 from Circulating Tumor DNA Enables Sensitive Detection of Actionable Gene Fusions and Rearrangements Across Cancer Types
Authors: Kasi Pashtoon M. , Lee Jessica K. , Pasquina Lincoln W. , Decker Brennan , Vanden Borre Pierre , Pavlick Dean C. , Allen Justin M. , Parachoniak Christine , Quintanilha Julia C. F. , Graf Ryon P. , Schrock Alexa B. , Oxnard Geoffrey R. , Lovly Christine M. , Tukachinsky Hanna , Subbiah Vivek
Published: February 2024

Supplementary Figures
Supplementary Table S1 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Table S1. Representativeness of study participants.
Supplementary Table S3 from Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial—Efficacy and Biomarker Discovery
Authors: Albain Kathy S. , Yau Christina , Petricoin Emanuel F. , Wolf Denise M. , Lang Julie E. , Chien A. Jo , Haddad Tufia , Forero-Torres Andres , Wallace Anne M. , Kaplan Henry , Pusztai Lajos , Euhus David , Nanda Rita , Elias Anthony D. , Clark Amy S. , Godellas Constantine , Boughey Judy C. , Isaacs Claudine , Tripathy Debu , Lu Janice , Yung Rachel L. , Gallagher Rosa I. , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Krings Gregor , Chen Yunn Yi , Potter David A. , Stringer-Reasor Erica , Blair Sarah , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Buxton Meredith , Clennell Julia L. , Sanil Ashish , Berry Scott , Asare Adam L. , Matthews Jeffrey B. , DeMichele Angela M. , Hylton Nola M. , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Symmans W. Fraser , van't Veer Laura J. , Yee Douglas , Berry Donald A. , Esserman Laura J.
Published: February 2024

Estimated pCR rates
Supplementary Figure S1 from Phase Ia/b Study of Giredestrant ± Palbociclib and ± Luteinizing Hormone-Releasing Hormone Agonists in Estrogen Receptor–Positive, HER2-Negative, Locally Advanced/Metastatic Breast Cancer
Authors: Jhaveri Komal L. , Bellet Meritxell , Turner Nicholas C. , Loi Sherene , Bardia Aditya , Boni Valentina , Sohn Joohyuk , Neilan Tomas G. , Villanueva-Vázquez Rafael , Kabos Peter , García-Estévez Laura , López-Miranda Elena , Pérez-Fidalgo J. Alejandro , Pérez-García Jose M. , Yu Jiajie , Fredrickson Jill , Moore Heather M. , Chang Ching-Wei , Bond John W. , Eng-Wong Jennifer , Gates Mary R. , Lim Elgene
Published: February 2024

Figure S1.
Best confirmed response by specific baseline ESR1 mutation: single-agent giredestrant ±LHRH agonist cohorts (A) and giredestrant +palbociclib ±LHRH agonist cohorts (B).
Supplementary Table S1 from Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial—Efficacy and Biomarker Discovery
Authors: Albain Kathy S. , Yau Christina , Petricoin Emanuel F. , Wolf Denise M. , Lang Julie E. , Chien A. Jo , Haddad Tufia , Forero-Torres Andres , Wallace Anne M. , Kaplan Henry , Pusztai Lajos , Euhus David , Nanda Rita , Elias Anthony D. , Clark Amy S. , Godellas Constantine , Boughey Judy C. , Isaacs Claudine , Tripathy Debu , Lu Janice , Yung Rachel L. , Gallagher Rosa I. , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Krings Gregor , Chen Yunn Yi , Potter David A. , Stringer-Reasor Erica , Blair Sarah , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Buxton Meredith , Clennell Julia L. , Sanil Ashish , Berry Scott , Asare Adam L. , Matthews Jeffrey B. , DeMichele Angela M. , Hylton Nola M. , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Symmans W. Fraser , van't Veer Laura J. , Yee Douglas , Berry Donald A. , Esserman Laura J.
Published: February 2024

Representativeness of Study Participants
Supplementary Methods S1 from Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial—Efficacy and Biomarker Discovery
Authors: Albain Kathy S. , Yau Christina , Petricoin Emanuel F. , Wolf Denise M. , Lang Julie E. , Chien A. Jo , Haddad Tufia , Forero-Torres Andres , Wallace Anne M. , Kaplan Henry , Pusztai Lajos , Euhus David , Nanda Rita , Elias Anthony D. , Clark Amy S. , Godellas Constantine , Boughey Judy C. , Isaacs Claudine , Tripathy Debu , Lu Janice , Yung Rachel L. , Gallagher Rosa I. , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Krings Gregor , Chen Yunn Yi , Potter David A. , Stringer-Reasor Erica , Blair Sarah , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Buxton Meredith , Clennell Julia L. , Sanil Ashish , Berry Scott , Asare Adam L. , Matthews Jeffrey B. , DeMichele Angela M. , Hylton Nola M. , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Symmans W. Fraser , van't Veer Laura J. , Yee Douglas , Berry Donald A. , Esserman Laura J.
Published: February 2024

Using Contemporary Controls and Adjusting for Time Trends in I-SPY2: The Time Machine
Supplementary Figure S1 from Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial—Efficacy and Biomarker Discovery
Authors: Albain Kathy S. , Yau Christina , Petricoin Emanuel F. , Wolf Denise M. , Lang Julie E. , Chien A. Jo , Haddad Tufia , Forero-Torres Andres , Wallace Anne M. , Kaplan Henry , Pusztai Lajos , Euhus David , Nanda Rita , Elias Anthony D. , Clark Amy S. , Godellas Constantine , Boughey Judy C. , Isaacs Claudine , Tripathy Debu , Lu Janice , Yung Rachel L. , Gallagher Rosa I. , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Krings Gregor , Chen Yunn Yi , Potter David A. , Stringer-Reasor Erica , Blair Sarah , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Buxton Meredith , Clennell Julia L. , Sanil Ashish , Berry Scott , Asare Adam L. , Matthews Jeffrey B. , DeMichele Angela M. , Hylton Nola M. , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Symmans W. Fraser , van't Veer Laura J. , Yee Douglas , Berry Donald A. , Esserman Laura J.
Published: February 2024

Kaplan-Meier survival plot of pCR vs. non-pCR in both trebananib and control arms
Supplementary Table S1 from Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial
Authors: Gatz Susanne A. , Harttrampf Anne C. , Brard Caroline , Bautista Francisco , André Nicolas , Abbou Samuel , Rubino Jonathan , Rondof Windy , Deloger Marc , Rübsam Marc , Marshall Lynley V. , Hübschmann Daniel , Nebchi Souad , Aerts Isabelle , Thebaud Estelle , De Carli Emilie , Defachelles Anne Sophie , Paoletti Xavier , Godin Robert , Miah Kowser , Mortimer Peter G.S. , Vassal Gilles , Geoerger Birgit
Published: February 2024

List of genes explored retrospectively for any kind of genetic alterations
Supplementary Table S4 from TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Bessede Alban , Peyraud Florent , Besse Benjamin , Cousin Sophie , Cabart Mathilde , Chomy François , Rey Christophe , Lara Oren , Odin Ophélie , Nafia Imane , Vanhersecke Lucile , Barlesi Fabrice , Guégan Jean-Philippe , Italiano Antoine
Published: February 2024

Supplementary Table 4. Characteristics of patients from the BIP study analyzed by plasma proteomics.
Supplementary Table S4 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Treatment exposure by PD-L1 subgroup (PD-L1 safety population).
Supplementary Table S3 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Summary of adverse events of any cause in the PD-L1, tTMB, and overall safety populations.
Supplementary Table S2 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Representativeness of study participants.
Supplementary Table S1 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Baseline patient demographics and disease characteristics for the PD-L1 and tTMB BEPs and the ITT population.
Supplementary Material S1 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Plain Language Summary
Supplementary Figure S8 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Prevalence of PD-L1 expression on TC and IC in the PD-L1 BEP. *Includes patients whose tumors had <1% PD-L1 expression on TCs or ICs, but not absolute zero.
Supplementary Figure S4 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Subgroup analysis of confirmed ORR by PD-L1 TC and IC expression for (A) durvalumab plus tremelimumab plus EP versus EP and (B) durvalumab plus EP versus EP. In each panel, the shaded band shows the confidence interval for the ITT population; circle sizes are proportional to the number of responses. Groups are not plotted when there are ≤5 responses across both arms.
Supplementary Figure S3 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Subgroup analysis of PFS by PD-L1 TC and IC expression for (A) durvalumab plus tremelimumab plus EP versus EP and (B) durvalumab plus EP versus EP. In each panel, the shaded band shows the confidence interval for the ITT population; circle sizes are proportional to the number of events.
Supplementary Figure S11 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Relationship between PD-L1 expression and tTMB score. (A) Box plots showing the distribution of tTMB score in patients by PD-L1 subgroup; (B) Venn diagram showing overlap between the tTMB ≥10 mut/Mb and PD-L1 TC or IC ≥1% subgroups. Percentages are calculated from the PD-L1 and tTMB BEP, i.e., patients who had both a PD-L1 and a tTMB result (n=275); samples from 171 patients had tTMB ≥10 mut/Mb and/or PD-L1 TC or IC ≥1%, while samples from 104 patients (37.8%) had both tTMB <10 mut/Mb and PD-L1 TC and IC <1%.
Supplementary Figure S1 from Durvalumab ± Tremelimumab + Platinum-Etoposide in Extensive-Stage Small Cell Lung Cancer (CASPIAN): Outcomes by PD-L1 Expression and Tissue Tumor Mutational Burden
Authors: Paz-Ares Luis , Garassino Marina Chiara , Chen Yuanbin , Reinmuth Niels , Hotta Katsuyuki , Poltoratskiy Artem , Trukhin Dmytro , Hochmair Maximilian J. , Özgüroğlu Mustafa , Ji Jun Ho , Statsenko Galina , Conev Nikolay , Bondarenko Igor , Havel Libor , Losonczy György , Xie Mingchao , Lai Zhongwu , Godin-Heymann Nadia , Mann Helen , Jiang Haiyi , Shrestha Yashaswi , Goldman Jonathan W.
Published: February 2024

Sample flow for biomarker analysis.
Supplementary Table S1 from Development of a Practical Nomogram for Personalized Anemia Management in Patients Treated with Ataxia Telangiectasia and Rad3-related Inhibitor Camonsertib
Authors: Rosen Ezra , Yap Timothy A. , Lee Elizabeth K. , Højgaard Martin , Mettu Niharika B. , Lheureux Stephanie , Carneiro Benedito A. , Plummer Ruth , Fretland Adrian J. , Ulanet Danielle , Xu Yi , McDougall Robin , Koehler Maria , Fontana Elisa
Published: February 2024

Supplementary Table S1. Treatment regimens evaluated in TRESR.
Supplementary Tables 1 from Functional Contribution and Clinical Implication of Cancer-Associated Fibroblasts in Glioblastoma
Authors: Galbo Phillip M. , Madsen Anne Tranberg , Liu Yang , Peng Mou , Wei Yao , Ciesielski Michael J. , Fenstermaker Robert A. , Graff Sarah , Montagna Cristina , Segall Jeffrey E. , Sidoli Simone , Zang Xingxing , Zheng Deyou
Published: February 2024

Tables S1-S10
Supplementary Table S4 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

Listing of patients by outcomes
Supplementary Table S1 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

Representativeness of study participants
Supplementary Figure S3 from A Phase Ib Study of the DNA-PK Inhibitor Peposertib Combined with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Romesser Paul B. , Capdevila Jaume , Garcia-Carbonero Rocio , Philip Tony , Fernandez Martos Carlos , Tuli Richard , Rodriguez-Gutierrez Almudena , Kuipers Mirjam , Becker Andreas , Coenen-Stass Anna , Sarholz Barbara , You Xiaoli , Miller Eric D.
Published: February 2024

Mean peposertib plasma concentration-time profiles after single- and multiple-dose administration
Supplementary Table S3 from A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non–small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics
Authors: Hummelink Karlijn , Tissier Renaud , Bosch Linda J.W. , Krijgsman Oscar , van den Heuvel Michel M. , Theelen Willemijn S.M.E. , Damotte Diane , Goldwasser François , Leroy Karen , Smit Egbert F. , Meijer Gerrit A. , Thommen Daniela S. , Monkhorst Kim
Published: February 2024

Patient characteristics and treatment outcomes for training and validation cohorts. P-values were calculated by Mann-Whitney, Fisher exact or linear-by-linear association tests.
Supplementary Fig. S3 from A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non–small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics
Authors: Hummelink Karlijn , Tissier Renaud , Bosch Linda J.W. , Krijgsman Oscar , van den Heuvel Michel M. , Theelen Willemijn S.M.E. , Damotte Diane , Goldwasser François , Leroy Karen , Smit Egbert F. , Meijer Gerrit A. , Thommen Daniela S. , Monkhorst Kim
Published: February 2024

Correlation of the PD-1T signature with the Tumor Inflammation Signature (TIS). Correlation of the PD-1T signature and the TIS in the validation cohort (n=42).
Supplementary Fig. S2 from A Dysfunctional T-cell Gene Signature for Predicting Nonresponse to PD-1 Blockade in Non–small Cell Lung Cancer That Is Suitable for Routine Clinical Diagnostics
Authors: Hummelink Karlijn , Tissier Renaud , Bosch Linda J.W. , Krijgsman Oscar , van den Heuvel Michel M. , Theelen Willemijn S.M.E. , Damotte Diane , Goldwasser François , Leroy Karen , Smit Egbert F. , Meijer Gerrit A. , Thommen Daniela S. , Monkhorst Kim
Published: February 2024

Predictive accuracy of PDCD1 gene expression.
Figure S1-S14, Table S1-S2 & S4-S6 from Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach
Authors: Schott Courtney R. , Koehne Amanda L. , Sayles Leanne C. , Young Elizabeth P. , Luck Cuyler , Yu Katherine , Lee Alex G. , Breese Marcus R. , Leung Stanley G. , Xu Hang , Shah Avanthi Tayi , Liu Heng-Yi , Spillinger Aviv , Behroozfard Inge H. , Marini Kieren D. , Dinh Phuong T. , Pons Ventura María V. , Vanderboon Emma N. , Hazard Florette K. , Cho Soo-Jin , Avedian Raffi S. , Mohler David G. , Zimel Melissa , Wustrack Rosanna , Curtis Christina , Sirota Marina , Sweet-Cordero E. Alejandro
Published: February 2024

Supplementary figures and tables
Supplementary Table S6 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Common SASP profile transcripts used in this study
Supplementary Table S5 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Authors: Coakley Maria , Villacampa Guillermo , Sritharan Prithika , Swift Claire , Dunne Kathryn , Kilburn Lucy , Goddard Katie , Pipinikas Christodoulos , Rojas Patricia , Emmett Warren , Hall Peter , Harper-Wynne Catherine , Hickish Tamas , Macpherson Iain , Okines Alicia , Wardley Andrew , Wheatley Duncan , Waters Simon , Palmieri Carlo , Winter Matthew , Cutts Rosalind J. , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C.
Published: February 2024

Rate of concordance and discordance between RaDaR and dPCR assays that tracked one or two variants, by sample
Supplementary Table S4 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Authors: Coakley Maria , Villacampa Guillermo , Sritharan Prithika , Swift Claire , Dunne Kathryn , Kilburn Lucy , Goddard Katie , Pipinikas Christodoulos , Rojas Patricia , Emmett Warren , Hall Peter , Harper-Wynne Catherine , Hickish Tamas , Macpherson Iain , Okines Alicia , Wardley Andrew , Wheatley Duncan , Waters Simon , Palmieri Carlo , Winter Matthew , Cutts Rosalind J. , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C.
Published: February 2024

Representativeness of the study population
Supplementary Table S1 from Comparison of Circulating Tumor DNA Assays for Molecular Residual Disease Detection in Early-Stage Triple-Negative Breast Cancer
Authors: Coakley Maria , Villacampa Guillermo , Sritharan Prithika , Swift Claire , Dunne Kathryn , Kilburn Lucy , Goddard Katie , Pipinikas Christodoulos , Rojas Patricia , Emmett Warren , Hall Peter , Harper-Wynne Catherine , Hickish Tamas , Macpherson Iain , Okines Alicia , Wardley Andrew , Wheatley Duncan , Waters Simon , Palmieri Carlo , Winter Matthew , Cutts Rosalind J. , Garcia-Murillas Isaac , Bliss Judith , Turner Nicholas C.
Published: February 2024

Characteristics of the ChemoNear patient population selected for pilot study.
Supplementary Figure S8 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

ANGPTL4 is necessary to drive senescence in palbociclib treated A549 cells
Supplementary Figure S7 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

ANGPTL4 is the most widely expressed and highly enriched transcript in treated cells compared to untreated cells
Supplementary Figure S6 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Palbociclib does not induce DNA damage in senescent LS8817 cells
Supplementary Figure S4 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Metabolome profiles of LS8817tetONFMDM2 undergoing cell cycle exit and geroconversion
Supplementary Figure S14 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Abemaciclib induced changes in FOXP3+ TILs in individual patients
Supplementary Figure S13 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Quantification of the Abemaciclib induced changes in CD4+ TILs in each patient
Supplementary Figure S1 from Therapy-Induced Senescence Contributes to the Efficacy of Abemaciclib in Patients with Dedifferentiated Liposarcoma
Authors: Gleason Caroline E. , Dickson Mark A. , Klein (Dooley) Mary E. , Antonescu Cristina R. , Gularte-Mérida Rodrigo , Benitez Marimar , Delgado Juliana I. , Kataru Raghu P. , Tan Mark Wei Yi , Bradic Martina , Adamson Travis E. , Seier Kenneth , Richards Allison L. , Palafox Marta , Chan Eric , D'Angelo Sandra P. , Gounder Mrinal M. , Keohan Mary Louise , Kelly Ciara M. , Chi Ping , Movva Sujana , Landa Jonathan , Crago Aimee M. , Donoghue Mark T.A. , Qin Li-Xuan , Serra Violetta , Turkekul Mesruh , Barlas Afsar , Firester Daniel M. , Manova-Todorova Katia , Mehrara Babak J. , Kovatcheva Marta , Tan Nguan Soon , Singer Samuel , Tap William D. , Koff Andrew
Published: February 2024

Demographics of patients enrolled in phase II clinical trial of abemaciclib in dedifferentiated liposarcoma
Data from Clinical Benefit of Avapritinib in KIT-Mutant Gastrointestinal Stromal Tumors: A Post Hoc Analysis of the Phase I NAVIGATOR and Phase I/II CS3007–001 Studies
Authors: Heinrich Michael C. , Zhang Xinhua , Jones Robin L. , George Suzanne , Serrano César , Deng Yanhong , Bauer Sebastian , Cai Shirong , Wu Xin , Zhou Yongjian , Tao Kaixiong , Zheng Zhichao , Zhang Jun , Cui Yuehong , Cao Hui , Wang Meining , Hu Jin , Yang Jason , Li Jian , Shen Lin
Published: February 2024

AbstractPurpose:
The efficacy of the selective KIT/PDGFRA inhibitor avapritinib (300 mg once daily) was explored in patients with non–PDGFRA-mutant gastrointestinal stromal tumors (GISTs) from the phase I NAVIGATOR and phase I/II CS3007–001 trials.
Patients and Methods:
Adults with unresectable/metastatic, KIT-only-mutant GISTs and progression following ≥1 tyrosine kinase inhibitors (TKIs) were included in this post hoc analysis. Baseline mutational status was identified in tumor and plasma. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent radiology review per modified RECIST v1.1 in patients harboring KIT activation-loop mutations (KIT exons 17 or 18) without ATP binding-pocket mutations (KIT exons 13 or 14; ALposABPneg), and other KIT mutations (OTHERS).
Results:
Sixty KIT ALposABPneg and 100 KIT OTHERS predominantly heavily pretreated patients (61.3% with ≥3 prior TKIs) were included. ORR was significantly higher in KIT ALposABPneg than KIT OTHERS patients (unadjusted: 26.7% vs. 12.0%; P = 0.0852; adjusted: 31.4% vs. 12.1%; P = 0.0047). Median PFS (mPFS) was significantly longer in KIT ALposABPneg patients compared with KIT OTHERS patients (unadjusted: 9.1 vs. 3.5 months; P = 0.0002; adjusted: 9.1 vs. 3.4 months; P < 0.0001), and longer in second- versus later-line settings (19.3 vs. 5.6–10.6 months). Benefit with avapritinib was observed in patients with KIT exon 9 mutations in the ≥4 line settings (mPFS: 5.6 and 3.7 months for 4 line and >4 line, respectively).
Conclusions:
Avapritinib showed greater antitumor activity in patients with GISTs harboring KIT ALposABPneg mutations versus KIT OTHERS, and may be considered in the former subpopulation. Patients with KIT exon 9 mutations may also benefit in ≥4 line settings.
Data from TROP2 Is Associated with Primary Resistance to Immune Checkpoint Inhibition in Patients with Advanced Non–Small Cell Lung Cancer
Authors: Bessede Alban , Peyraud Florent , Besse Benjamin , Cousin Sophie , Cabart Mathilde , Chomy François , Rey Christophe , Lara Oren , Odin Ophélie , Nafia Imane , Vanhersecke Lucile , Barlesi Fabrice , Guégan Jean-Philippe , Italiano Antoine
Published: February 2024

AbstractPurpose:
Mechanisms of primary resistance to inhibitors of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling axis in non–small cell lung cancer (NSCLC) are still poorly understood. While some studies suggest the involvement of trophoblast cell surface antigen 2 (TROP2) in modulating tumor cell resistance to therapeutic drugs, its specific role in the context of PD-1/PD-L1 axis blockade is not definitively established.
Experimental Design:
We performed high-throughput analysis of transcriptomic data from 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy in two large randomized clinical trials. To confirm our results at the protein level, we complemented this transcriptional approach by performing a multiplex immunofluorescence analysis of tumor tissue samples as well as a proteomic profiling of plasma.
Results:
We observed a significant association of TROP2 overexpression with worse progression-free survival and overall survival on PD-L1 blockade, independent of other prognostic factors. Importantly, we found increased TROP2 expression to be predictive of survival in patients treated with atezolizumab but not chemotherapy. TROP2 overexpression was associated with decreased T-cell infiltration. We confirmed these results at the proteomic level both on tumor tissue and in plasma.
Conclusions:
Our results suggest an important contribution of TROP2 expression to the primary resistance to PD-L1 blockade in NSCLC. TROP2-biomarker–based strategy may be relevant in selecting patients with NSCLC who are more likely to benefit from a combination of immunotherapy and an anti-TROP2 agent.
Tsyn-Seq: a T-cell Synapse–Based Antigen Identification Platform
Authors: Jin Yimei , Miyama Takahiko , Brown Alexandria , Hayase Tomo , Song Xingzhi , Singh Anand K. , Huang Licai , Flores Ivonne I. , McDaniel Lauren K. , Glover Israel , Halsey Taylor M. , Prasad Rishika , Chapa Valerie , Ahmed Saira , Zhang Jianhua , Rai Kunal , Peterson Christine B. , Lizee Gregory , Karmouch Jennifer , Hayase Eiko , Molldrem Jeffrey J. , Chang Chia-Chi , Tsai Wen-Bin , Jenq Robert R.
Published: February 2024

Tools for genome-wide rapid identification of peptide–major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell–APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library.

See related Spotlight by Makani and Joglekar, p. 515.
FIGURE 7 from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R.
Published: February 2024

Concurrent Pim and FLT3 inhibitor treatment activates GSK-3β, and GSK-3β inhibitor abrogates c-Myc and Mcl-1 downregulation. A, Ba/F3-ITD cells and FLT3-ITD AML patient blasts were treated with gilteritinib and/or AZD1208, or DMSO control, and expression of c-Myc, Mcl-1, p-GSK-3α,β (S9/S21), GSK-3α,β and β-actin or vinculin loading control at serial time points was measured by immunoblotting. Data in A are shown graphically in B. C, Ba/F3-ITD and MV4-11 cells and FLT3-ITD AML patient blasts were treated with gilteritinib and/or AZD1208, or DMSO control, with and without the GSK-3β inhibitor TC G-24 at 20 nM, and expression of c-Myc, Mcl-1, p-GSK-3α,β (S9/S21), GSK-3α,β and β-actin or vinculin loading control was measured at serial time points by immunoblotting. Data in C are shown graphically in D.
FIGURE 2 from Pim Kinase Inhibitors Increase Gilteritinib Cytotoxicity in FLT3-ITD Acute Myeloid Leukemia Through GSK-3β Activation and c-Myc and Mcl-1 Proteasomal Degradation
Authors: Lee Jonelle K. , Chatterjee Aditi , Scarpa Mario , Bailey Christopher M. , Niyongere Sandrine , Singh Prerna , Mustafa Ali Moaath K. , Kapoor Shivani , Wang Yin , Silvestri Giovannino , Baer Maria R.
Published: February 2024

TP-3654 enhances efficacy of gilteritinib in vivo. NRG mice injected intravenously with MV4-11-luc cells were treated with gilteritinib and/or TP-3654, or vehicle control, with first treatment day defined as day 1. A, Serial images of mice in first experiment, treated with gilteritinib 7.5 mg/kg and/or TP-3654 50 mg/kg, or vehicle control, once every other day for three doses, followed by 2 days rest, each week. B, Changes in photon intensity, measured by bioluminescence imaging, over time, with P = 0.0043, comparing gilteritinib and TP-3654 combination versus gilteritinib alone on day 60 by two-way ANOVA with Sidak multiple comparison test. C, Survival curves, with P = 0.0027 by Kaplan–Meier analysis. Median survival was 51, 44, 51, and 65 days for mice treated with vehicle, TP-3654, gilteritinib, and gilteritinib and TP-3654 combination, respectively. D, Serial images of mice in second experiment, treated with gilteritinib 15 mg/kg and/or TP-3654 50 mg/kg, or vehicle control, daily for 5 days each week. E, Change in photon intensity, measured by bioluminescence imaging, over time, with P < 0.0001, comparing gilteritinib and TP-3654 combination versus gilteritinib alone by day 35 by two-way ANOVA.