bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract A048: Novel murine models of ARID1A and PBRM1-deficient cholangiocarcinoma for preclinical discovery and development
Authors: Conboy Caitlin B. , Tomlinson Jennifer L. , Watkins Ryan D. , Millender Jayla T. , Carlson Danielle M. , Smoot Rory L. , Robertson Keith D. , Gores Greg J.
Published: December 2023

Genes encoding SWI/SNF chromatin remodeling complex subunits are recurrently mutated across human cancers. In cholangiocarcinoma (CCA), AT-rich interaction domain-1A (ARID1A) and polybromo-1 (PBRM1) loss of function mutations occur in approximately 18 and 10% of cases respectively. Yet our mechanistic understanding and ability to therapeutically exploit ARID1A and PBRM1 deficiency are immature. Genetically accurate preclinical models are needed to define the role of ARID1A and PBRM1 and test therapeutic approaches in CCA. Analysis of human CCA tumors showed that loss of function mutations in ARID1A and PBRM1 frequently co-occur with each other and with PI3K/AKT pathway activation. Therefore, we developed novel murine models of cholangiocarcinoma initiated by Arid1a knockout or dual Arid1a/Pbrm1 knockout in the context of AKT activation, employing a surgical biliary transfection method for somatic gene editing with CRISPR/Cas9. Mice with cholangiocyte Arid1a knockout and AKT activation (AAC) or dual Arid1a/Pbrm1 knockout and AKT activation (APAC) formed numerous liver tumors within 8 months. Histologically, tumors were predominantly CCA and mixed HCC/CCA, with a similar spectrum of tumors across AAC and APAC mice. Gene editing with CRISPR/Cas9 was confirmed at the DNA level, and loss of protein expression was confirmed in tumor cells by immunohistochemistry. Similar to human CCA, many tumors were densely infiltrated with cancer-associated fibroblasts and a variable degree of CD45+ immune cells. To generate scalable models for preclinical testing, tumors from AAC and APAC mice were dissociated to create cell lines for in vitro studies and propagated by orthotopic transplantation for in vivo studies. Cell lines and orthotopic tumors were validated and retained the genetic features and histologic characteristics of the parental tumors.   Collectively these studies have produced a suite of novel, well-characterized, genetically relevant mouse models of epigenetic dysregulation in CCA due to ARID1A and PBRM1 deficiency, which can be used broadly for discovery research and preclinical testing of novel treatment approaches.

Citation Format: Caitlin B. Conboy, Jennifer L. Tomlinson, Ryan D. Watkins, Jayla T. Millender, Danielle M. Carlson, Rory L. Smoot, Keith D. Robertson, Greg J. Gores. Novel murine models of ARID1A and PBRM1-deficient cholangiocarcinoma for preclinical discovery and development [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A048.
Abstract A108: Metabolic oriented treatment: efficacy of sr59230a 𝜷3-adrenergic receptor antagonist, and sr plus buformin® in Ewing sarcoma
Authors: Banella Cristina , Zocca Laura , Boaretto Alessia , Mattei Gianluca , Mola Marina , Ballerini Lara , Nicla Lorito , Tondo Annalisa , Calvani Maura
Published: December 2023

Purpose of study: Metabolic targeted therapies may represent an innovative strategy in Ewing sarcoma (ES).

Introduction: Ewing sarcoma (ES) is highly aggressive round cell mesenchymal neoplasm, most often occurring in children and young adults. Metabolic peculiarities of ES cells are indeed involved in tumor growth, survival and resistance to therapy. We have further investigated apoptotic role of 𝜷3-adrenergic receptor (𝜷3-AR) SR59230A (SR) antagonist for its ability to reduce cells viability due increased oxidative stress, now we underline the metabolic role of SR.

Materials & Methods: The metabolic profile after SR administration in A673 ES cell model was studied using the Seahorse XF Analyzer. Viability was evaluated with MTS. Changes in gene expression was evaluated with RNA sequencing. Western blot analysis and Immunofluorescence was performed for redox signature and metabolic alteration. Ros production was assessed by flow cytometry.

Results: Quantification of transcript abundance using Salmon in A673 after SR treatment showed decrease in response to reactive oxygen species, increase of Thioredoxin Interacting Protein (TXNIP) inhibits the antioxidative function of thioredoxin, moreover reduced glucose uptake, consequently decrease NADPH/NADP resulting in the accumulation of ROS coincident with a decrease of GLUT1, SOD2, TrDX an increase of LC3IIA protein expression. SR enhances A673 pyruvate dependency, and decrease glyco and mito ATP production rate, more over observed under glucose deprivation. To inibite mitochondrial ATP production rate we proposed the metabolic oriented treatment with Buformin® (BUF) an oral antidiabetic drug of the biguanide class.  BUF completely shut down mitochondrial respiration acted on complex I of electron transport chain (ETC). Buf combined with SR decrease ATP production and up-regulated ROS production in ES cells.

Conclusion: SR antagonist of 𝜷3-AR  and combination of SR with BUF could be an innovative therapeutic option to raise awareness ES.

Citation Format: Cristina Banella, Laura Zocca, Alessia Boaretto, Gianluca Mattei, Marina Mola, Lara Ballerini, Lorito Nicla, Annalisa Tondo, Maura Calvani. Metabolic oriented treatment: efficacy of sr59230a 𝜷3-adrenergic receptor antagonist, and sr plus buformin® in Ewing sarcoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A108.
Abstract A132: Pathological analysis of a newly established immunocompetent mice with full Hpv16 genome integration
Authors: Li Xue , Kothari Aditi , Rehmani Hina , Yarbrough Wendell , Isaeva Natalia
Published: December 2023

Human papillomaviruses (HPV) are associated with both benign and malignant epithelial lesions. High-risk HPV subtype HPV 16 is the causative agent of cervical and the majority of oropharyngeal squamous cell carcinomas. Despite the continuous increase in the disease burden, mechanisms and pathways of HPV16-induced cancer growth are not fully understood, thus leading to suboptimal treatment.  In last decades, several transgenic mouse models were developed, helped tremendously to study HPV-induced carcinogenesis. However, all existent HPV transgenic mice were targeted early genes expression driven by an artificial promoter and did not encompass the functionality of the whole HPV genome, including the upstream regulatory region (URR) that contains HPV promoters, regulatory elements, and a replication origin, limited our ability to investigate HPV-associated malignant transformation and the role of host factors in this process. Therefore, we generated HPV16 transgenic mouse by using CRISPR/Cas9-mediated genome editing to insert the full-length HPV16 genome into the Rosa26 locus. Two founder mice, with single HPV copy and with tandem HPV integration, were used to establish mouse colonies. Interestingly, regardless of HPV copy number, ~50% of the HPV knock-in mice exhibited early death during the first 2 weeks after birth, while survived pups were significantly smaller than the same age wild-type mice, and had severe hair loss. Intriguingly, the growth retardant and hair loss phenotype in the HPV16 knock-in mice disappeared in ~4 weeks, most likely indicating that viral genes compromise specific stages of mouse development. We evaluated the expression of HPV genes during development, in different mouse organs, and in established fibroblasts and epithelial cell cultures.   Our newly established HPV16 knock-in mouse model provides viral gene expression from natural viral promoters offering an essential basis to explore the role of cellular factors in HPV-driven pathologies.

Citation Format: Xue Li, Aditi Kothari, Hina Rehmani, Wendell Yarbrough, Natalia Isaeva. Pathological analysis of a newly established immunocompetent mice with full Hpv16 genome integration [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A132.
Abstract A151: Establishing assays to investigate combinations of fractioned radiotherapy with DNA damage response agents in vitro and in vivo to enable investigation of radiosensitization and improved anti-tumour responses
Authors: Bell Charlotte , Brown Stewart , Cantrell Amy , Farrington Paul , Garcia Miguel , Hodgson Ben , Ho Yin Xin , Jordan Allan , Katopodi Theoni , Kendrew Jane , Neo Wen Hao , Thomson Stuart , Walker Graeme E , Wright Emily
Published: December 2023

Introduction: Radiotherapy is a main treatment modality for multiple cancer types, with approximately half of all cancer patients receiving radiotherapy as part of their treatment regimen. In addition to direct cytotoxic effects on cancer cells, it is now appreciated that radiosensitization using specific drugs inhibiting DNA damage response (DDR) pathways can enhance the sensitivity of tissues or cells to radiation therapy.  Establishing assays to screen for potential radiosensitizing compounds is therefore valuable to inform drug discovery research.

Methods: The MDA-MB-436 human breast cancer cell line was selected for assay optimization. DDR inhibitors of DNA-dependent protein kinase (DNA-PK) (AZD7648) and Poly-(ADP-Ribose)-Polymerase (PARP) (niraparib) were used as tool radiosensitizing compounds, as these proteins play key roles in the repair of radiation-induced DNA double strand breaks. Effects on cell viability, cell cycle progression and DDR biomarkers were determined under a variety of irradiation (IR) and compound conditions.  In parallel, in vivo validation experiments were performed.

Results and Conclusions: Both AZD7648 and niraparib radiosensitize MDA-MB-436 cells to IR treatment. A dose of 2 Gray (Gy) reduced the observed anti-proliferative compound IC50 compared to IR treatment or compound treatment alone. Furthermore, combined treatment of 2 Gy IR with either DDR inhibitor induces S-phase cell cycle arrest and increases cell death. Analysis of DDR biomarkers confirms their induction by radiotherapy in combination with DDR inhibitors. Similar changes to DDR biomarker expression were also observed in the in vivo xenograft mouse model.  In summary, in vitro and in vivo assays have been established to investigate radiosensitization through the combination of IR and DDR inhibitors. Furthermore, these assays can identify novel compounds acting via a synergistic mechanism.

Citation Format: Charlotte Bell, Stewart Brown, Amy Cantrell, Paul Farrington, Miguel Garcia, Ben Hodgson, Yin Xin Ho, Allan Jordan, Theoni Katopodi, Jane Kendrew, Wen Hao Neo, Stuart Thomson, Graeme E Walker, Emily Wright. Establishing assays to investigate combinations of fractioned radiotherapy with DNA damage response agents in vitro and in vivo to enable investigation of radiosensitization and improved anti-tumour responses [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A151.
Abstract B073: Characterization of selective, allosteric inhibitors of human XRN1
Authors: Lockbaum Gordon J , Sickmier E. Allen , Sparling Brian A , Knockenhauer Kevin , Holt Nicholas , Liu Julie , Lynes Maureen M , Grigoriu Simina , Duncan Kenneth W , Copeland Robert A , Boriack-Sjodin P. Ann
Published: December 2023

Background: 5′→3′ exoribonuclease 1 (XRN1) plays an important role in innate immunity by preventing double stranded RNA (dsRNA) accumulation. In addition, XRN1 has emerged as a potential target for drug discovery efforts as tumors with high interferon signaling are sensitive to XRN1 loss using genetic tools. To date, no XRN1-selective inhibitors have been disclosed. This study details characterization of two small-molecule inhibitors of XRN1, 3’-5’ adenosine diphosphate (pAp) and Compound 1, through biochemical, biophysical, and structural analysis.

Materials and Methods: Enzymatic and biophysical assays for XRN1 were developed, and characterization of XRN1 inhibitors was performed. To enable structure-based drug design, novel constructs of human XRN1 were designed and characterized for both catalytic activity and compound binding using biochemical and biophysical methods. In addition, cocrystal structures of XRN1 were determined for each inhibitor.

Results: pAp was found to be a potent, RNA-competitive inhibitor of XRN1 dsRNA degradation with similar activity for XRN2. Cocrystal structures of XRN1 with pAp confirm the nucleotide analog binds in the active site of the enzyme. Enzymatic and biophysical techniques indicate Compound 1 is also a substrate-competitive inhibitor with single-digit micromolar affinity for XRN1. However, Compound 1 is highly selective for XRN1 and does not bind or inhibit XRN2. High-resolution crystal structures indicate that Compound 1 binds in an allosteric binding site, confirming the mechanism of inhibition and selectivity profile determined by in vitro assays.

Conclusions: This work demonstrates XRN1 can be selectively inhibited by small-molecule inhibitors. Human XRN1 structures provide a tool for structure-based drug design efforts against this compelling oncology target.Conflict of Interests: All authors are current or former employees and shareholders of Accent Therapeutics, Inc.

Citation Format: Gordon J Lockbaum, E. Allen Sickmier, Brian A Sparling, Kevin Knockenhauer, Nicholas Holt, Julie Liu, Maureen M Lynes, Simina Grigoriu, Kenneth W Duncan, Robert A Copeland, P. Ann Boriack-Sjodin. Characterization of selective, allosteric inhibitors of human XRN1 [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B073.
Abstract LB_B17: Single-cell analysis of dynamic remodeling of radiated TNBC cells
Authors: Ku Minhee , Kim Jin Sung , Koom Woong Sub , Yang Jaemoon
Published: December 2023

The dynamic rearrangement of the cellular cytoskeletal network and changes in cellular stiffness play crucial roles in the progression of malignant tumors, including those with invasive and metastatic traits. Despite the acknowledged connections, the inherent complexity of cancer and the various microenvironments that individual cells experience during treatment have hindered comprehensive investigations into therapeutic responses, particularly at the individual cell level. Notably, the emergence of large DNA damage-induced cells following radiotherapy in the challenging-to-treat triple-negative breast cancer (TNBC) subtype suggests potential concurrent alterations in cellular mechanics. This study dives into the complex interplay among radiation therapy, cytoskeletal architecture, and cellular stiffness at the level of individual cells. By utilizing atomic force microscopy (AFM) as a quantitative and non-invasive technique, we discerned how cancer cells respond to radiation treatment based on their cytoskeletal properties. Our findings revealed a clear correlation between radiation therapy and disruptions in cytoskeletal integrity, along with a simultaneous increase in cellular stiffness. These observed changes could potentially indicate impending cell death or a reduced tendency for metastasis. Building on these insights, we propose that assessing cytoskeletal features through AFM holds potential for tailoring personalized radiation therapy approaches, depending on the distinct responses exhibited by cancer cells post-treatment. This shift in approach, guided by mechanics, underscores the capacity to enhance treatment effectiveness while minimizing unintended damage. By shedding light on the intricate interplay between radiation-induced cellular responses and mechanical properties, this study lays the foundation for innovative strategies that leverage cytoskeletal attributes to customize and optimize therapeutic interventions for TNBC and potentially other malignancies.

Citation Format: Minhee Ku, Jin Sung Kim, Woong Sub Koom, Jaemoon Yang. Single-cell analysis of dynamic remodeling of radiated TNBC cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_B17.
Abstract A095: Rural disparities in telemedicine use among cancer survivors during the COVID-19 pandemic
Authors: Lee Minjee , Tsai Meng-Han
Published: December 2023

Background: The COVID-19 pandemic has led to significant changes in the delivery of healthcare across the world, including the widespread adoption of telemedicine. This study examined the prevalence of telemedicine use by rurality and determined whether rurality was associated with its use among cancer survivors in the United States (US). Methods: The 2021 National Health Interview Survey (NHIS) was used to examine the use of telemedicine among cancer survivors during the pandemic. Our primary outcome is telemedicine use and rurality is our main exposure of interest.  Other covariates of interest include demographics, health-related factors (number of comorbidities, self-rated health), and types of cancer history. Descriptive statistics and multiple logistic regression models were used to examine the mentioned association. Results: Among 27,500 eligible cancer survivors, 51.6% (14,140 participants) of them reported telemedicine use. The use of telemedicine varied by rurality, with 41.4% of rural cancer survivors using telemedicine compared to 58.4% of cancer survivors in large central metropolitan areas (p<0.001). Rural cancer survivors had significantly lower odds of using telemedicine during the pandemic compared to metropolitan cancer survivors. Cancer survivors residing in rural were 0.58 times less likely (95% CI, 0.43 to 0.78) and cancer survivors residing in medium and small metropolitan areas were 0.72 times less likely (95% CI, 0.56 to 0.93) to report telemedicine use compared to cancer survivors residing in large central metropolitan areas. Conclusion: Significant rural disparities in telemedicine use were evident among cancer survivors. Rural cancer survivors were less likely to use telemedicine during the COVID-19 pandemic. To ensure equitable access to telemedicine, continued reimbursement for telemedicine services, but additional efforts are needed to improve access to and utilization of healthcare for rural cancer survivors.

Citation Format: Minjee Lee, Meng-Han Tsai. Rural disparities in telemedicine use among cancer survivors during the COVID-19 pandemic [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A095.
Abstract B108: Racial disparities in survival among oral cavity and pharynx cancer patients treated with immunotherapy: Insights from the US National Cancer Database (NCDB)
Authors: Yang Danting , Karanth Shama
Published: December 2023

Purpose: Survival rates for oral cavity and oropharynx cancers vary by race, with Non-Hispanic(NH)-Black patients experiencing relatively lower survival rates compared to NH-White patients. While the potential for improving survival with immunotherapy has been demonstrated in clinical trials, it remains unclear whether racial disparities persist in patients treated with this novel approach. We aimed to evaluate the association between race and all-cause mortality among oral and pharynx cancer patients who received immunotherapy. Methods: This study utilized the National Cancer Database (NCDB) to investigate racial disparities in survival after immunotherapy among patients diagnosed with oral cavity and pharynx cancers between 2013 and 2017. Multivariable Cox proportional hazards models were employed to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) by race/ethnicity. Results: The study cohort included 7,714 patients, consisting of 7,011 NH-White patients and 703 NH-Black patients. During the follow-up period, mortality occurred in 45.5% of NH-White patients and 59.5% of NH-Black patients. After adjusting for sociodemographic, clinical, and treatment factors, NH-Black patients had a higher risk of death compared to NH-White patients (HR: 1.24; 95% CI: 1.11, 1.38). Additionally, the study found no significant differences in the interaction between race and Charlson-Deyo comorbidity score or race and area-level median income. Conclusion: This study suggests that urgent action is needed to address these disparities to improve outcomes for NH-Black patients with oral cavity and pharynx cancers.

Citation Format: Danting Yang, Shama Karanth. Racial disparities in survival among oral cavity and pharynx cancer patients treated with immunotherapy: Insights from the US National Cancer Database (NCDB) [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B108.
Abstract C038: BRCA2 haploinsufficiency driven neoplastic events in the fallopian tube epithelia
Authors: Ravix Jovanka , Paudel Iru , Sowamber Ramlogan , Pulivendala Gauthami , Lombard David , George Sophia
Published: December 2023

One in 70 women will develop ovarian cancer over their lifetime in the US and epithelial ovarian cancer (EOC) remains the deadliest gynecological cancer. EOC is a heterogenous disease and high-grade serous carcinoma (HGSOC) is the most common histotype. It is genetically unstable due to pathogenic variants in BRCA1, BRCA2, PALB2, ATM, and RAD51 genes involved in DNA damage response and repair which are part of the hereditary breast and ovarian cancer syndrome (HBOC). In women with a BRCA1 or BRCA2 mutation undergoing risk-reducing surgery, 3-17% have pre-neoplastic and neoplastic lesions in their fallopian tubes. These lesions, known as serous tubal intra-epithelial carcinoma (STIC), display differential loss of heterozygosity of BRCA1/2. New insights into BRCA2 function could provide novel opportunities for preventative interventions in individuals with this mutation, and perhaps new treatment opportunities for HGSC associated with BRCA2 heterozygosity.  We have identified distinct metabolic and mitochondrial deficits in BRCA2 mutation carriers compared to BRCA1 carriers and non-carriers. Fallopian tube epithelial cell lines derived from BRCA2 mutation carriers showed increased levels of mitochondrial respiration and activity followed by BRCA1 mutation carriers and non-carriers. Transmission electron microscopy of BRCA2 mutation carriers showed increased disrupted mitochondrial networks when compared to wild type, suggesting that mutation status may contribute to increased mitochondrial fission. These observations reveal an entirely new aspect of BRCA2 biology and further studies will disaggregate the effects of BRCA2 on mitochondrial function, versus DNA damage repair. Ultimately, this work will provide new insight into the adaptive changes within FT cells which promote neoplastic transformation and inform how high-grade serous carcinoma (HGSC) cells distinctively respond to microenvironmental stimuli.

Citation Format: Jovanka Ravix, Iru Paudel, Ramlogan Sowamber, Gauthami Pulivendala, David Lombard, Sophia George. BRCA2 haploinsufficiency driven neoplastic events in the fallopian tube epithelia [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C038.
Abstract C046: Aryl hydrocarbon receptor activity may lead to the downstream transcription of several genes relevant to prostate cancer progression, apoptosis and lipid metabolism
Authors: Khamit-Kush Kofi K. , Powell Joann B. , Handy Jeffrey A. , Bowen Nathan J. , Wu Daqing , Odero-Marah Valerie
Published: December 2023

The aryl hydrocarbon receptor (AhR) is a nuclear transcription factor and xenobiotic sensor reported to mediate diet-induced obesity and is both upregulated and constitutively active in high-grade prostate cancer. AhR activity has also been reported to contribute to proliferation and potentially disease progression in C4-2 cells (Powell et al. 2015). To determine if the aryl hydrocarbon receptor mediates transcription of genes pertinent to cancer progression, we performed an RNA-seq analysis in C4-2 AhR knockdown cells and the vehicle control. When a fold-change cutoff of ±1.5 and an adjusted p-value (p-adj) <0.05 were used, data analyses revealed several differentially expressed genes (DEGS), i.e. LEPROT, CHAC1/2, GDF11/15, CDKN2, FAS, FASTKD, ATF1/3, CCNL2, and CCNG2 with known functions involving the cell cycle, apoptosis, epigenetic modifications, tumor aggressiveness, and interestingly – lipid metabolism. Recent evidence demonstrates significant changes in the expression profile of many of these genes in response to treatment with chemotherapeutics, specifically bromocriptine (Wu et al 2023). In murine models AhR has been shown to promote diet-induced obesity coupled with metabolic dysregulation leading to obesity, which has been reported to cause malignant behaviors in prostate cancer. Leptin, a pleiotropic obesity-associated adipokine, is significantly overexpressed in mCRPC tissues. Our lab previously reported an integrative bioinformatics analysis using TCGA data (n=498) to explore the role of AHR and leptin receptor (LEPR) in prostate cancer, which revealed AHR and LEPR mRNA expression positively correlate in a subset of prostate cancer patients (P<0.05, Pearson: 0.68, R^2=0.46). We also confirmed AhR inhibits bortezomib and docetaxel -mediated apoptosis of C4-2 cells (data not shown). Further understanding of the potential interactions between metabolism and drug treatment should lead to a better understanding of the complex network of factors influencing prostate cancer progression and lead to more effective therapeutics for patients.

Citation Format: Kofi K. Khamit-Kush, Joann B. Powell, Jeffrey A. Handy, Nathan J. Bowen, Daqing Wu, Valerie Odero-Marah. Aryl hydrocarbon receptor activity may lead to the downstream transcription of several genes relevant to prostate cancer progression, apoptosis and lipid metabolism [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C046.
Abstract C049: Genomic correlates with ancestry in lung squamous cell carcinoma
Authors: Jain Sejal , Yao Alexandria , Momen-Heravi Fatemeh , Allen-Gipson Diane , Zhang Xiaoyang , Henick Brian S. , Carrot-Zhang Jian , Taylor Alison M.
Published: December 2023

Outcome data from lung squamous cell carcinoma (SCC) show significantly lower overall and progression-free survival in Black patients. However, whether any genomic factors correlate with race and ancestry in this lung SCC, and whether this may contribute to disparities, has not been elucidated. We analyzed clinically annotated genomic data from 501 lung SCC tumor samples in the Cancer Genome Atlas (TCGA), with available ancestry admixture data. Here, we analyzed clinical data, gene expression profiles, mutations, and copy number changes to identify significantly differential events between tumors from patients of European (EUR) or African (AFR) ancestry. In tumors from AFR patients, we identified more frequent gain of chromosome arm 8q and/or the chr8q24 locus, where the oncogene MYC and its enhancers are located. 8q24 gain is associated both with global AFR ancestry and local AFR ancestry. Furthermore, expression of MYC targets is significantly increased in AFR samples relative to EUR samples, all of which suggest a role for the MYC pathway in differential cancer progression. MYC activity correlates with decreased immune infiltration and gene signaling, and patients with AFR ancestry are more likely to have decreased immune infiltrate and pathway activity. Our findings are consistent with observations in prostate cancer; this is the first study to find MYC enhancer amplification correlating with African ancestry in lung SCC. We are currently testing additional cohorts, including AACR GENIE, to validate these findings. Future studies will elucidate patient-specific treatment modalities.

Citation Format: Sejal Jain, Alexandria Yao, Fatemeh Momen-Heravi, Diane Allen-Gipson, Xiaoyang Zhang, Brian S. Henick, Jian Carrot-Zhang, Alison M. Taylor. Genomic correlates with ancestry in lung squamous cell carcinoma [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C049.
Supplementary Figure 2 from Competing Engagement of β-arrestin Isoforms Balances IGF1R/p53 Signaling and Controls Melanoma Cell Chemotherapeutic Responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Trocoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard
Published: December 2023

Effect of β-arrestin imbalance on MDM2 localization
Figure S2 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

CircDDIT4 acts as an anti-oncogene in PCa.
Supplementary Figure 7 from Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis
Authors: Green Benjamin L. , Gamble Lauren A. , Diggs Laurence P. , Nousome Darryl , Patterson Jesse C. , Joughin Brian A. , Gasmi Billel , Lux Stephanie C. , Samaranayake Sarah G. , Miettinen Markku , Quezado Martha , Hernandez Jonathan M. , Yaffe Michael B. , Davis Jeremy L.
Published: December 2023

Heatmap of CIBERSORTx data from Figure 3A.
Supplementary Figure 3 from Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis
Authors: Green Benjamin L. , Gamble Lauren A. , Diggs Laurence P. , Nousome Darryl , Patterson Jesse C. , Joughin Brian A. , Gasmi Billel , Lux Stephanie C. , Samaranayake Sarah G. , Miettinen Markku , Quezado Martha , Hernandez Jonathan M. , Yaffe Michael B. , Davis Jeremy L.
Published: December 2023

GSEA of T cell-specific gene sets related to (A) activation, costimulation, and (B) exhaustion comparing SRC to NEP.
Figure S5 from BACH1 Loss Exerts Antitumor Effects on Mantle Cell Lymphoma Cells via Inducing a Tumor-Intrinsic Innate Immune Response and Cell-Cycle Arrest
Authors: Li Guilan , Feng Min , Zhang Ziting , Liu Jiangyuan , Zhang Han
Published: December 2023

Figure S5 shows the knockdown efficiency of ZBTB20 or HBP1 in MCL cells as well as their growth rates.
Table S5 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

Primers for ChIP-qPCR used in this study.
Table S4 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

Antibodies used for ChIP-seq/ChIP-qPCR assays in this study.
Table S3 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

TaqMan RT-qPCR primers and probes used in this study.
Data from FBXO24 suppresses breast cancer tumorigenesis by targeting LSD1 for Ubiquitination
Authors: Dong Bo , Song Xiang , Wang Xinzhao , Dai Tao , Wang Jianlin , Yu Zhiyong , Deng Jiong , Evers B. Mark , Wu Yadi
Published: December 2023

Abstract
LSD1, a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function remains unknown. To gain a better understanding of LSD1 degradation, we conducted an unbiased siRNA screening targeting all the human SCF family E3 ligases. Our screening identified FBXO24 as a genuine E3 ligase that ubiquitinates and degrades LSD1. As a result, FBXO24 inhibits LSD1-induced tumorigenesis and functions as a tumor suppressor in breast cancer cells. Moreover, FBXO24 exhibits an inverse correlation with LSD1 and is associated with a favorable prognosis in breast cancer patient samples. Taken together, our study uncovers the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.
Implications: Our study provides comprehensive characterization of the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.
Data from Generating a Murine PTEN Null Cell Line to Discover the Key Role of p110β-PAK1 in Castration-Resistant Prostate Cancer Invasion
Authors: Wang Haizhen , Zhou Yu , Chu Chen , Xiao Jialing , Zheng Shanshan , Korpal Manav , Korn Joshua M. , Penaloza Tiffany , Drake Richard R. , Gan Wenjian , Gao Xueliang
Published: December 2023

Abstract
Although androgen deprivation treatment often effectively decreases prostate cancer, incurable metastatic castration-resistant prostate cancer (CRPC) eventually occurs. It is important to understand how CRPC metastasis progresses, which is not clearly defined. The loss of PTEN, a phosphatase to dephosphorylate phosphatidylinositol 3,4,5-trisphosphate in the PI3K pathway, occurs in up to 70% to 80% of CRPC. We generated a mouse androgen-independent prostate cancer cell line (PKO) from PTEN null and Hi-Myc transgenic mice in C57BL/6 background. We confirmed that this PKO cell line has an activated PI3K pathway and can metastasize into the femur and tibia of immunodeficient nude and immunocompetent C57BL/6 mice. In vitro, we found that androgen deprivation significantly enhanced PKO cell migration/invasion via the p110β isoform-depended PAK1-MAPK activation. Inhibition of the p110β-PAK1 axis significantly decreased prostate cancer cell migration/invasion. Of note, our analysis using clinical samples showed that PAK1 is more activated in CRPC than in advanced prostate cancer; high PAK1/phosphorylated-PAK1 levels are associated with decreased survival rates in patients with CRPC. All the information suggests that this cell line reflects the characteristics of CRPC cells and can be applied to dissect the mechanism of CRPC initiation and progression. This study also shows that PAK1 is a potential target for CRPC treatment.
Implications:
This study uses a newly generated PTEN null prostate cancer cell line to define a critical functional role of p110β-PAK1 in CRPC migration/invasion. This study also shows that the p110β-PAK1 axis can potentially be a therapeutic target in CRPC metastasis.
Supplementary Table S1 from A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study
Authors: Vageli Dimitra P. , Doukas Panagiotis G. , Shah Rema , Boyi Trinithas , Liu Christina , Judson Benjamin L.
Published: December 2023

Supplementary Table S1 shows OSCC patients’ characteristics, social history for risk factors and histology of oral lesion that saliva and blood (serum) were collected.
Supplementary Tables from Long-Read Sequencing Reveals Alternative Splicing-Driven, Shared Immunogenic Neoepitopes Regardless of SF3B1 Status in Uveal Melanoma
Authors: Yao Tengteng , Zhang Zhe , Li Qian , Huang Rui , Hong Yanhong , Li Chen , Zhang Feng , Huang Yingying , Fang Yan , Cao Qin , Jin Xiaoliang , Li Chunliang , Wang Zefeng , Lin Xinhua (James) , Li Lingjie , Wei Wu , Wang Zhaoyang , Shen Jianfeng
Published: December 2023

Supplementary Tables and legends
Supplementary Table S8 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Nucleotide sequence
Supplementary Table S6 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Clinicopathological characteristics of Cohort ⅤI patients with urothelial cell carcinoma of the bladder
Supplementary Table S2 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Clinicopathological characteristics of Cohort Ⅱ patients with urothelial cell carcinoma of the bladder
Supplementary Table S13 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Association of expressions of VISTA with PD-1/PD-L1 in Cohort Ⅱ UCB Patients
Supplementary Table S10 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Primers used for qRT-PCR
Supplementary Figure S9 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Combination (combo) of VISTA mAb 13F3/sODN-dsRNA with CD8+ T cell depletion induced TME changes in MB49 tumors
Supplementary Figure S7 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Combination (combo) of VISTA mAb 13F3 with sODN-dsRNA induced TME changes in MB49 tumors
Supplementary Figure S3 from Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant
Authors: Wang Bo , Ou Ziwei , Zhong Wenlong , Huang Lin , Liao Wenjian , Sheng Yiyu , Guo Zhixing , Chen Junyu , Yang Wenjuan , Chen Ke , Huang Xiaodong , Yang Tenghao , Lin Tianxin , Huang Jian
Published: December 2023

Flow cytometry gating strategy
Supplemental Figure 10 from Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor Cell Therapy
Authors: Nowicki Theodore S. , Peters Cole W. , Quiros Crystal , Kidd Conner K. , Kawakami Moe , Klomhaus Alexandra M. , Baselga-Carretero Ignacio , Kaplan-Lefko Paula , Macabali Mignonette H. , Perez Garcilazo Ivan , Berent-Maoz Beata , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

. No association between CD8 secreted IFN- FSI and clinical response to transgenic TCR T cell therapy. (A) CD8 secreted IFN- FSI levels showed no significant difference between clinical responders and non-responders to TCR T cell therapy (unpaired t-test), and showed no significant correlation with peak change in tumor burden (B) nor overall survival (C) by Pearson’s r.
Supplementary Table S2 from A Metabolic Gene Survey Pinpoints Fucosylation as a Key Pathway Underlying the Suppressive Function of Regulatory T Cells in Cancer
Authors: Pinioti Sotiria , Sharma Himal , Flerin Nina C. , Yu Qian , Tzoumpa Amalia , Trusso Cafarello Sarah , De Bousser Elien , Callewaert Nico , Oldenhove Guillaume , Schlenner Susan , Thienpont Bernard , Garg Abhishek D. , Di Matteo Mario , Mazzone Massimiliano
Published: December 2023

Antibodies for Flow Cytometry
Supplementary Table S1 from A Metabolic Gene Survey Pinpoints Fucosylation as a Key Pathway Underlying the Suppressive Function of Regulatory T Cells in Cancer
Authors: Pinioti Sotiria , Sharma Himal , Flerin Nina C. , Yu Qian , Tzoumpa Amalia , Trusso Cafarello Sarah , De Bousser Elien , Callewaert Nico , Oldenhove Guillaume , Schlenner Susan , Thienpont Bernard , Garg Abhishek D. , Di Matteo Mario , Mazzone Massimiliano
Published: December 2023

gRNA sequences used for electroporation and lentiviral transduction and primers used for PCR are listed below
Figure S1 from Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1− Dysfunctional State
Authors: Roetman Jessica J. , Erwin Megan M. , Rudloff Michael W. , Favret Natalie R. , Detrés Román Carlos R. , Apostolova Minna K.I. , Murray Kristen A. , Lee Ting-Fang , Lee Youngmin A. , Philip Mary
Published: December 2023

SST and TST are functional in the acute infection context.
Figure S2 from A Metabolic Gene Survey Pinpoints Fucosylation as a Key Pathway Underlying the Suppressive Function of Regulatory T Cells in Cancer
Authors: Pinioti Sotiria , Sharma Himal , Flerin Nina C. , Yu Qian , Tzoumpa Amalia , Trusso Cafarello Sarah , De Bousser Elien , Callewaert Nico , Oldenhove Guillaume , Schlenner Susan , Thienpont Bernard , Garg Abhishek D. , Di Matteo Mario , Mazzone Massimiliano
Published: December 2023

Additional evidence of the validation of positive and negative regulators of Foxp3. Related to Figure 2. (A-B) Deletion efficiency of Slc35c1 with the 2 guides, measured by PCR. (C-G) Deletion efficiency for the targeted genes in iTregs after electroporation by PCR. Samples correspond to the results shown in Fig. 2C and 2D. (H) MFI Foxp3 (relative to sgNT) 7 days after electroporation of each of the targets. (I) Percentage of Foxp3 expression by flow cytometry 7 days after electroporation with two independent gRNAs for Slc35c1. (J) Representative flow chart of the Foxp3 expression on sgNT control iTregs, sgSlc35c1 and sgAdss iTregs 7 days upon electroporation. In vitro data are the pooled data of least three independent experiments. Statistical analysis was performed using paired (Fig. S2A-G) or unpaired (Fig. S2H-I) two-tailed t-test and are represented as mean ± SEM (ns, p > 0.05, * p  0.05, ** p  0.01 and *** p  0.001).
Data file Reactome_analysis from A Metabolic Gene Survey Pinpoints Fucosylation as a Key Pathway Underlying the Suppressive Function of Regulatory T Cells in Cancer
Authors: Pinioti Sotiria , Sharma Himal , Flerin Nina C. , Yu Qian , Tzoumpa Amalia , Trusso Cafarello Sarah , De Bousser Elien , Callewaert Nico , Oldenhove Guillaume , Schlenner Susan , Thienpont Bernard , Garg Abhishek D. , Di Matteo Mario , Mazzone Massimiliano
Published: December 2023

Data file Reactome_analysis
Supplementary Figure 2 from Antigen Priming Induces Functional Reprogramming in iNKT Cells via Metabolic and Epigenetic Regulation: An Insight into iNKT Cell-Based Antitumor Immunotherapy
Authors: Zhang Huimin , Chen Sanwei , Zhang Yuwei , Tian Chenxi , Pan Jun , Wang Yu , Bai Shiyu , Wu Qielan , Su Miya , Xie Di , Fu Sicheng , Li Shuhang , Zhang Jing , Chen Yusheng , Zhu Shasha , Qian Yeben , Bai Li
Published: December 2023

A, Procedure for TCR priming in vitro. B-C, Frequencies of IFN+ (B), GzmA+, and GzmB+ (C) naïve and TCR-primed iNKT cells restimulated with anti-CD3 plus anti-CD28 antibodies as indicated in (A) (n = 3). Data are represented as mean ± SD. Student’s t test was used to determine statistical significance (*P<0.05, ***P<0.001, n.s., not significant).
Supplementary Table S4 from Antitumor Immune Responses in B2M-Deficient Cancers
Authors: Torrejon Davis Y. , Galvez Mildred , Abril-Rodriguez Gabriel , Campbell Katie M. , Medina Egmidio , Vega-Crespo Agustin , Kalbasi Anusha , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

CIBERSORTx output.
Supplementary Table S1 from Antitumor Immune Responses in B2M-Deficient Cancers
Authors: Torrejon Davis Y. , Galvez Mildred , Abril-Rodriguez Gabriel , Campbell Katie M. , Medina Egmidio , Vega-Crespo Agustin , Kalbasi Anusha , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Panel of immune markers for dendritic cell, myeloid cell and T cell characterization by flow cytometry.
Supplementary Data Legends from Antitumor Immune Responses in B2M-Deficient Cancers
Authors: Torrejon Davis Y. , Galvez Mildred , Abril-Rodriguez Gabriel , Campbell Katie M. , Medina Egmidio , Vega-Crespo Agustin , Kalbasi Anusha , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Supplementary legends.
Figure S6 from Antitumor Immune Responses in B2M-Deficient Cancers
Authors: Torrejon Davis Y. , Galvez Mildred , Abril-Rodriguez Gabriel , Campbell Katie M. , Medina Egmidio , Vega-Crespo Agustin , Kalbasi Anusha , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

Bempegaldesleukin to reverse resistance in JAK1-deficient tumors. (A) In vivo tumor growth curves for MC38 JAK1-KO tumors treated with 0.8 mg/kg intravenous bempegaldesleukin every 9 days x 2 doses, or anti-PD-1 therapy, or the combination. Data represented as mean ± SEM from an n of 4 per group. The arrow indicates the days of treatment with bempegaldesleukin or when anti -PD-1 therapy was started. Dunnett multiple comparisons tests for control versus anti-PD-1, or bempegaldesleukin, or bempegaldesleukin plus anti-PD-1. ns, not significant; ****, P < 0.0001. (B) The measure of MHC class I expression by flow cytometry after IFNγ stimulation in MC38 WT, JAK1-KO and B2M-KO. JAK1-KO maintains its MHC class I basal expression upon IFNγ. Histograms represent changes in MFI by flow cytometry.
Figure S5 from Antitumor Immune Responses in B2M-Deficient Cancers
Authors: Torrejon Davis Y. , Galvez Mildred , Abril-Rodriguez Gabriel , Campbell Katie M. , Medina Egmidio , Vega-Crespo Agustin , Kalbasi Anusha , Comin-Anduix Begoña , Ribas Antoni
Published: December 2023

(A) T cell subsets and (B) myeloid and dendritic cell subsets in MC38 with and without B2M expression. Differences in the infiltration of immune cells in MC38 WT and B2M-KO tumors. Tumors were collected on day 9 (two doses of isotype or a-PD-1) and day 16 (four doses of isotype or a-PD-1). (C) Numbers of CD8+ T, CD4+ T and NK cells per gram in MC38 WT and B2M-KO tumors. Mean ± SEM, Unpaired t test, n = 6. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001*.