bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S4 from Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML
Authors: Letson Christopher T. , Balasis Maria E. , Newman Hannah , Binder Moritz , Vedder Alexis , Kinose Fumi , Ball Markus , Kruer Traci , Quintana Ariel , Lasho Terra L. , Finke Christy M. , Almada Luciana L. , Grants Jennifer M. , Zhang Guolin , Fernandez-Zapico Martin E. , Gaspar-Maia Alexandre , Lancet Jeffrey , Komrokji Rami , Haura Eric , Sallman David A. , Reuther Gary W. , Karsan Aly , Rix Uwe , Patnaik Mrinal M. , Padron Eric
Published: August 2023

Supplemental Figure 4 contains data related to miR-33a regulation in BETi treated cells.
Supplementary Tables 1-3 from Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors
Authors: Vieito Maria , Moreno Victor , Spreafico Anna , Brana Irene , Wang Judy S. , Preis Meir , Hernández Tatiana , Genta Sofia , Hansen Aaron R. , Doger Bernard , Galvao Vladimir , Lenox Laurie , Brown Regina J. , Kalota Anna , Mehta Jaydeep , Pastore Friederike , Patel Bharvin , Mistry Pankaj , Gu Junchen , Lauring Josh , Patel Manish R.
Published: August 2023

Supplementary Tables 1-3
Supplementary Table S6 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Metastatic Sites Involved Prior to HER2-Directed Therapy.
Supplementary Table S2 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Representativeness of Study Participants.
Supplementary Methods S1 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Supplemental Methods
Supplementary Figure S7 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Baseline biopsies from a patient demonstrating significant intra-patient heterogeneity with diffusely HER2+ and PD-L1– primary tumor and HER2– but PD-L1 CPS 100 retroperitoneal lymph node with neuroendocrine differentiation.
Supplementary Figure S4 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Early change in tumor-matched maxVAF in patients who received induction trastuzumab and pembrolizumab stratified by 6 month PFS (n=16 evaluable).
Supplementary Figure S10 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Identifying intratumor clonal selection and associated resistance mechanisms. a, Inferred tumor clones paired pre-treatment and post-cycle 2 CAPOX + trastuzumab scRNA-seq demonstrates rapid clearance of highly ERBB2 expression (red) clones, while many lower expressing clones persisted and even expanded. Contraction at the on-treatment timepoint reflects their RECIST response at their initial follow up imaging timepoint, demonstrating that patient 3, who had the highest ERBB2 expression, had the deepest and most durable response. b, Pre- and on-treatment size and fold-change of clones identified in pane a ordered by pre-treatment ERBB2 expression. Clonal expansion was most commonly seen in clones with low ERBB2 expression and was associated with a resistance program derived by GeneVector. c, MT1H, MT1E, MT2A, and MSMB expression were significantly higher in clones expanding despite CAPOX + trastuzumab (TC) versus both contracting clones after TC as well as expanding clones after CAPOX (C) only, suggesting association with therapeutic resistance. d, The resistance program strongly correlated with the CAPOX+trastuzumab clones, and poorly with CAPOX-treated clones, as intended.
Supplementary Figure S1 from Determinants of Survival with Combined HER2 and PD-1 Blockade in Metastatic Esophagogastric Cancer
Authors: Maron Steven B. , Chatila Walid , Walch Henry , Chou Joanne F. , Ceglia Nicholas , Ptashkin Ryan , Do Richard Kinh Gian , Paroder Viktoriya , Pandit-Taskar Neeta , Lewis Jason S. , Biachi De Castria Tiago , Sabwa Shalom , Socolow Fiona , Feder Lara , Thomas Jasmine , Schulze Isabell , Kim Kwanghee , Elzein Arijh , Bojilova Viktoria , Zatzman Matthew , Bhanot Umesh , Nagy Rebecca J. , Lee Jeeyun , Simmons Marc , Segal Michal , Ku Geoffrey Yuyat , Ilson David H. , Capanu Marinela , Hechtman Jaclyn F. , Merghoub Taha , Shah Sohrab , Schultz Nikolaus , Solit David B. , Janjigian Yelena Y.
Published: August 2023

Consort diagram of HER2-directed therapy patient cohorts.
Data from Tumor-Agnostic Precision Medicine from the AACR GENIE Database: Clinical Implications
Authors: Gouda Mohamed A. , Nelson Blessie E. , Buschhorn Lars , Wahida Adam , Subbiah Vivek
Published: August 2023

Abstract
Biomarker-driven cancer therapy has revolutionized precision oncology. With a better understanding of tumor biology, tissue-agnostic targets have been characterized and explored, which ultimately led to therapeutics with pan-cancer efficacy. To date, five molecular biomarkers have obtained FDA tissue-agnostic approval for targeted therapies and immunotherapies. Those include BRAFV600E mutations, RET fusions, NTRK fusions, high tumor mutation burden (TMB), and deficient mismatch repair/high microsatellite instability (dMMR/MSI-High). Herein, we have used data from AACR project GENIE to explore the clinico-genomic landscape of these alterations. AACR GENIE is a publicly accessible registry of genomic data from multiple collaborating cancer centers. Current database (version 13.0) includes sequencing data of 168,423 samples collected from patients with different cancers. We were able to identify BRAFV600E, RET fusions, NTRK fusions, and high TMB in 2.9%, 1.6%, 1.5%, and 15.2% of pan-cancer samples, respectively. In this article, we describe the distribution of those tissue-agnostic targets among different cancer types. In addition, we summarize the current prospect on the biology of these alterations and evidence on approved drugs, including pembrolizumab, dostarilmab, larotrectinib, entrectinib, selpercatinib, and dabrafenib/trametinib combination.
Data from Genomic Profiling of Radiation-Induced Sarcomas Reveals the Immunologic Characteristics and Its Response to Immune Checkpoint Blockade
Authors: Hong Dong-Chun , Yang Jing , Sun Cong , Liu Yuan-Tao , Shen Lu-Jun , Xu Bu-Shu , Que Yi , Xia Xiaojun , Zhang Xing
Published: August 2023

AbstractPurpose:
Radiation-induced sarcomas (RIS) have a poor prognosis and lack effective treatments. Its genome and tumor microenvironment are not well characterized and need further exploration.
Experimental Design:
Here, we performed whole-exome sequencing (WES) and mRNA sequencing (mRNA-seq) on patients with RIS and primary sarcomas (WES samples 46 vs. 48, mRNA-seq samples 16 vs. 8, mainly in head and neck), investigated the antitumor effect of programmed cell death protein 1 (PD-1) blockade in RIS patient-derived xenograft models, and analyzed clinical data of patients with RIS treated with chemotherapy alone or combined with an anti–PD-1 antibody.
Results:
Compared with primary sarcomas, RIS manifested different patterns of copy-number variations, a significantly higher number of predicted strong MHC-binding neoantigens, and significantly increased immune cell infiltration. Clinical data showed that the combinatorial use of chemotherapy and PD-1 blockade achieved a higher objective response rate (36.67% vs. 8.00%; P = 0.003), longer overall survival (31.9 months vs. 14.8 months; P = 0.014), and longer progression-free survival (4.7 months vs. 9.5 months; P = 0.032) in patients with RIS compared with single chemotherapy.
Conclusions:
Elevated genomic instability and higher immune cell infiltrations were found in RIS than in primary sarcomas. Moreover, higher efficacy of chemotherapy plus PD-1 blockade was observed in animal experiments and clinical practice. This evidence indicated the promising application of immune checkpoint inhibitors in the treatment of RIS.
Axicabtagene Ciloleucel in Combination with the 4–1BB Agonist Utomilumab in Patients with Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Results from ZUMA-11
Authors: Jain Michael D. , Miklos David B. , Jacobson Caron A. , Timmerman John M. , Sun Jennifer , Nater Jenny , Fang Xiang , Patel Ankit , Davis Madison , Heeke Darren , Trinh Tan , Mattie Mike , Neumann Frank , Kim Jenny J. , To Christina , Filosto Simone , Reshef Ran
Published: August 2023

Purpose:

Chimeric antigen receptor (CAR) T-cell therapies have shown clinical benefit for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL), yet approximately 60% of patients do not respond or eventually relapse. We investigated the safety and feasibility of the CD19-directed CAR T-cell therapy axicabtagene ciloleucel (axi-cel) in combination with the 4–1BB agonist antibody utomilumab as an approach to improve efficacy of CAR T-cell therapy.

Patients and Methods:

In phase 1 of the single-arm ZUMA-11 trial, patients with R/R LBCL received a single axi-cel infusion (target dose, 2 × 106 cells/kg) plus utomilumab 10 to 200 mg intravenously every 4 weeks for up to 6 months in a dose-escalation design. The primary endpoint was incidence of dose-limiting toxicities (DLT) with utomilumab. Key secondary endpoints were safety, antitumor activity, pharmacokinetics, and pharmacodynamics.

Results:

No DLTs were observed among patients treated with axi-cel and utomilumab (n = 12). Grade ≥3 adverse events occurred in 10 patients (83%); none were Grade ≥3 cytokine release syndrome or neurologic events. The objective response rate was 75% and seven patients (58%) had a complete response. Peak CAR T-cell levels increased in a utomilumab dose-dependent manner up to 100 mg. Patients who received utomilumab 100 mg had persistently increased CAR T cells on days 57 to 168 compared with other dose levels. Utomilumab was associated with dose-dependent increases in IL2, IFNγ, and IL10.

Conclusions:

Utomilumab-mediated 4–1BB agonism combined with axi-cel therapy had a manageable safety profile. Dual 4–1BB and CD28 costimulation is a feasible therapeutic approach that may enhance CAR T-cell expansion in patients with LBCL.
Table S1 from The Role of Protein Arginine Methyltransferases in Pathogenesis and Treatment of Digestive System Carcinoma
Authors: Wang Bin , Ding Dong , Zhang Xiaoan , Zhang Junxi , Zhang Huanhuan , Liu Xinxin , Chang Hui , Gao Zhan , Yu Zengli
Published: August 2023

Table S1 shows the application of PRMT inhibitors in gastrointestinal tumors.
Figure S2 from Bromo- and Extra-Terminal Domain Inhibitors Induce Mitochondrial Stress in Pancreatic Ductal Adenocarcinoma
Authors: Rana Manjul , Kansal Rita G. , Bisunke Bijay , Fang Jie , Shibata David , Bajwa Amandeep , Yang Jun , Glazer Evan S.
Published: August 2023

Figure s2
Supplementary Table S2 from Schlafen 11 (SLFN11) Kills Cancer Cells Undergoing Unscheduled Re-replication
Authors: Murai Junko , Ceribelli Michele , Fu Haiqing , Redon Christophe E. , Jo Ukhyun , Murai Yasuhisa , Aladjem Mirit I. , Thomas Craig J. , Pommier Yves
Published: August 2023

Results of HTS in K562+Vector and K562+WT SLFN11 cells
Supplementary Table S1 from Schlafen 11 (SLFN11) Kills Cancer Cells Undergoing Unscheduled Re-replication
Authors: Murai Junko , Ceribelli Michele , Fu Haiqing , Redon Christophe E. , Jo Ukhyun , Murai Yasuhisa , Aladjem Mirit I. , Thomas Craig J. , Pommier Yves
Published: August 2023

Results of HTS in CCRF-CEM parent and SLFN11-KO cells
Supplementary File 1 from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yong Sung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: August 2023

HTS data showing efficacy of different compounds as single agents.
Supplementary Figure 6 from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yong Sung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: August 2023

Supplementary Figure 6 shows that vinorelbine is also synergistic with trametinib in KRAS-mutant CRC 3D spheroids
Supplementary Figure 5 from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yong Sung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: August 2023

Supplementary Figure 5 shows that trametinib increases the intracellular accumulation of daunorubicin in KRAS-mutant CRC cells.
Supplementary Table S9 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Antibody-dependent cell-mediated cytotoxicities of MW282 mAb, 9MW2821, and enfortumab vedotin
Supplementary Figure 3 from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yong Sung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: August 2023

Supplementary Figure 3 shows that the combination of trametinib and vincristine inhibits tumor growth and reduces tumor weight in PDX C1138
Supplementary Figure 2 from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yong Sung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: August 2023

Supplementary Figure 2 shows that the combination of trametinib and vincristine reduces weight of CRC PDXs.
Supplementary Table S7 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Binding affinity of MW282 mAb, 9MW2821, and enfortumab vedotin based on enzyme linked immunosorbent assay
Supplementary Table S3 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Patient information for gastric cancer formalin-fixed paraffin-embedded samples
Supplementary Table S16 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Summary of pharmacokinetics studies in 9MW2821 and enfortumab vedotin in tumor-bearing mice
Supplementary Table S14 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Individual incidence of clinical observations
Supplementary Table S13 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

General hematological toxicity
Supplementary Table S12 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Toxicokinetic parameters of 9MW2821 in cynomolgus monkeys.
Supplementary Table S11 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Nectin-4 expression levels and in vitro cytotoxicity
Supplementary Fig.S8 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Antibody-dependent cell-mediated cytotoxicity of MW282 mAb, 9MW2821, and enfortumab vedotin (EV) measured by a cell-based reporter-gene assay.
Supplementary Fig.S7 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Binding affinity measured by Biolayer interferometry.
Supplementary Fig.S3 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Comparison of the structure of 9MW2821 and enfortumab vedotin.
Supplementary Fig.S2 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

Characterization of MW282 mAb, parental mAb of 9MW2821.
Supplementary Fig.S11 from Preclinical Evaluation of 9MW2821, a Site-Specific Monomethyl Auristatin E–based Antibody–Drug Conjugate for Treatment of Nectin-4–expressing Cancers
Authors: Zhou Wei , Fang Peng , Yu Dongan , Ren Hongyuan , You Meng , Yin Long , Mei Fei , Zhu Huikai , Wang Zhenzhen , Xu Hui , Cao Yuxia , Sun Xiaowei , Xu Xiaohong , Bi Jianjun , Wang Jin , Ma Lanping , Wang Xin , Chen Lin , Zhang Yongliang , Cen Xiaowei , Zhu Xi , Lou Liguang , Liu Datao , Tan Xiaoding , Yang Jinliang , Meng Tao , Shen Jingkang
Published: August 2023

The nectin-4 expression for BR1282
Supplementary Data from APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy
Authors: Xie Xuqin , Fan Chuanwen , Luo Bin , Zhang Jing , Jensen Lasse D. , Burman Jonas , Jönsson Carolin , Ljusberg Anna , Larsson Peter , Zhao Zengren , Sun Xiao-Feng
Published: August 2023

p53Wt_log2FC of genes
Figure S5 from APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy
Authors: Xie Xuqin , Fan Chuanwen , Luo Bin , Zhang Jing , Jensen Lasse D. , Burman Jonas , Jönsson Carolin , Ljusberg Anna , Larsson Peter , Zhao Zengren , Sun Xiao-Feng
Published: August 2023

Supplementary figure 5
Figure S3 from APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy
Authors: Xie Xuqin , Fan Chuanwen , Luo Bin , Zhang Jing , Jensen Lasse D. , Burman Jonas , Jönsson Carolin , Ljusberg Anna , Larsson Peter , Zhao Zengren , Sun Xiao-Feng
Published: August 2023

Supplementary figure 3
Figure S2 from APR-246 Enhances Colorectal Cancer Sensitivity to Radiotherapy
Authors: Xie Xuqin , Fan Chuanwen , Luo Bin , Zhang Jing , Jensen Lasse D. , Burman Jonas , Jönsson Carolin , Ljusberg Anna , Larsson Peter , Zhao Zengren , Sun Xiao-Feng
Published: August 2023

Supplementary figure 2
Data from Schlafen 11 (SLFN11) kills cancer cells undergoing unscheduled re-replication
Authors: Murai Junko , Ceribelli Michele , Fu Haiqing , Redon Christophe E. , Jo Ukhyun , Murai Yasuhisa , Aladjem Mirit I. , Thomas Craig J. , Pommier Yves
Published: August 2023

Abstract
SLFN11 is an increasingly prominent predictive biomarker and a molecular sensor for a wide range of clinical drugs: topoisomerases, PARP and replication inhibitors, and platinum derivatives. To expand the spectrum of drugs and pathways targeting SLFN11, we ran a high-throughput screen (HTS) with 1,978 mechanistically-annotated, oncology-focused compounds in two isogenic pairs of SLFN11-proficient and -deficient cells (CCRF-CEM and K562). We identified 29 hit compounds that selectively kill SLFN11-proficient cells, including not only previously known DNA-targeting agents, but also the neddylation inhibitor Pevonedistat (MLN-4924) and the DNA polymerase alpha inhibitor AHPN/CD437, which both induced SLFN11 chromatin recruitment. By inactivating cullin-ring E3 ligases, Pevonedistat acts as an anticancer agent partly by inducing unscheduled re-replication through supra-physiological accumulation of CDT1, an essential factor for replication initiation. Unlike the known DNA-targeting agents and AHPN/CD437 that recruit SLFN11 onto chromatin in 4 hours, Pevonedistat recruited SLFN11 at late time points (24 hours). While Pevonedistat induced unscheduled re-replication in SLFN11-deficient cells after 24 hours, the re-replication was largely blocked in SLFN11-proficient cells. The positive correlation between sensitivity to Pevonedistat and SLFN11 expression was also observed in non-isogenic cancer cells in three independent cancer cell databases (NCI-60, CTRP: Cancer Therapeutics Response Portal and GDSC: Genomic of Drug Sensitivity in Cancer). The present study reveals that, in addition to sensing stressed replication, SLFN11 blocks unscheduled re-replication provoked by Pevonedistat, which augments the anti-cancer effect of Pevonedistat. It also suggests SLFN11 as a potential predictive biomarker for Pevonedistat in ongoing and future clinical trials.
Data from Discordance of HER2 Expression and/or Amplification on Repeat Testing
Authors: DiPeri Timothy P. , Kong Kathleen , Varadarajan Kaushik , Karp Daniel D. , Ajani Jaffer A. , Pant Shubham , Press Michael F. , Piha-Paul Sarina A. , Dumbrava Ecaterina E. , Meric-Bernstam Funda
Published: August 2023

Abstract
We sought to assess discordance of HER2 status in patients with HER2 amplified/expressing solid tumors who underwent reevaluation of HER2 status. Patients with metastatic solid tumors and HER2 expression by immunohistochemistry (IHC) or amplification by fluorescent in situ hybridization (FISH)/next generation sequencing (NGS) on local testing underwent central HER2 IHC/FISH testing with either archival or fresh biopsies and were evaluated for discordance in HER2 status. 70 patients (12 cancer types) underwent central HER2 reevaluation, including 57 (81.4%) with a new biopsy. In 30 patients with HER2 3+ on local IHC, 21 (70.0%) were 3+, 5 (16.7%) were 2+, 2 (6.7%) were 1+, and 2 (6.7%) had 0 HER2 expression on central IHC. In 15 patients whose cancers were 2+ on local IHC, 2 (13.3%) were 3+, 5 (33.3%) were 2+, 7 (46.7%) were 1+, and 1 (6.7%) had 0 HER2 expression on central IHC. HER2 discordance was seen in 16 of 52 (30.8%) of patients with HER2 overexpression/amplification who underwent a new image-guided biopsy. Discordance was observed in 10 (33.3%) of 30 patients who received intervening HER2-targeted therapy and in 6 (23.8%) of 22 patients who did not. In the 8 patients who had central HER2 assessment from the same archival block used for local testing, none were discordant. Discordance of HER2 status is common in patients with tumors previously identified as HER2-expressing, especially in patients with HER2 2+ tumors. Repeat biomarker evaluation may have value when considering HER2-targeted therapies.
Data from Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer
Authors: Ghosh Susmita , Fan Fan , Powell Reid T. , Roszik Jason , Park Yongsung , Stephan Clifford , Sebastian Manu , Tan Lin , Sorokin Alexey V. , Lorenzi Philip L. , Kopetz Scott , Ellis Lee M. , Bhattacharya Rajat
Published: August 2023

Abstract
Mutations in KRAS are found in more than 50% of tumors from patients with metastatic colorectal cancer (mCRC). However, direct targeting of most KRAS mutations is difficult; even the recently developed KRASG12C inhibitors failed to show significant benefit in patients with mCRC. Single agents targeting MEK, a downstream mediator of RAS, have also been ineffective in CRC. To identify drugs that can enhance the efficacy of MEK inhibitors we performed unbiased high-throughput screening using CRC spheroids. We used trametinib as the anchor drug and examined combinations of trametinib with the National Cancer Institute Approved Oncology Library version 5. The initial screen, and following focused validation screens, identified vincristine as being strongly synergistic with trametinib. In vitro, the combination strongly inhibited cell growth, reduced clonogenic survival, and enhanced apoptosis compared to monotherapies in multiple KRAS-mutant CRC cell lines. Furthermore, this combination significantly inhibited tumor growth, reduced cell proliferation, and increased apoptosis in multiple KRAS-mutant patient-derived xenograft mouse models. In vivo studies using drug doses that reflect clinically achievable doses demonstrated that the combination was well tolerated by mice. We further determined that the mechanism underlying the synergistic effect of the combination was due to enhanced intracellular accumulation of vincristine associated with MEK inhibition. The combination also significantly decreased p-mTOR levels in vitro, indicating that it inhibits both RAS-RAF-MEK and PI3K-AKT-mTOR survival pathways. Our data thus provide strong evidence that the combination of trametinib and vincristine represents a novel therapeutic option to be studied in clinical trials for patients with KRAS-mutant mCRC.
Data from APR-246 enhances colorectal cancer sensitivity to radiotherapy
Authors: Xie Xuqin , Fan Chuanwen , Luo Bin , Zhang Jing , Jensen Lasse D. , Burman Jonas , Jonsson Carolin , Ljusberg Anna , Larsson Peter , Zhao Zengren , Sun Xiao-Feng
Published: August 2023

Abstract
p53 mutation is common and highly related to radiotherapy resistance in rectal cancer. APR-246, as a small molecule, can restore the tumor-suppressor function to mutant p53. There is no study on combining APR-246 with radiation in rectal cancer; therefore, we examined whether APR-246 sensitized colorectal cancer cells with different p53 status to radiation. The combination treatment had synergistic effects on HCT116p53-R248W/-(p53Mut) cells, followed by HCT116p53+/+(p53WT) cells, and exhibited an additive effect on HCT116p53-/-(p53Null) cells through inhibiting proliferation, enhancing reactive oxygen species, and apoptosis. The results were confirmed in zebrafish xenografts. Mechanistically, p53Mut and p53WT cells shared more activated pathways and differentially expressed genes following the combination treatment, compared to p53Null cells, although the combination treatment regulated individual pathways in the different cell lines. APR-246 mediated radio-sensitization effects through p53-dependent and -independent ways. The results may provide evidence for a clinical trial of the combination in rectal cancer patients.
Supplementary Figure 1 from Desmoglein 2 Functions as a Receptor for Fatty Acid Binding Protein 4 in Breast Cancer Epithelial Cells
Authors: Chen Dongmei , Wirth Keith M. , Kizy Scott , Muretta Joseph M. , Markowski Todd W. , Yong Peter , Sheka Adam , Abdelwahab Hisham , Hertzel Ann V. , Ikramuddin Sayeed , Yamamoto Masato , Bernlohr David A.
Published: August 2023

S1. DSC and DSG isoforms expressed in MCF-7 cells.
Supplementary Figure Legends 1-7 from Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: August 2023

S1. The western diet extensively reprograms Lgr5hi stem cells that expands with time and is reversible. This includes the TCA cycle and Oxphos pathways.S2. The western diet elevates and suppresses multiple pathways by 3 months, most persisting to 12 months, and reversible by switching to control diet.S3. The western diet suppresses expression of a large number of genes encoding subunits of each of the 5 complexes of mitochondrial electron transport.S4. Mouse genotyping identified presence of the wild-type, or heterozygous or homozygous conditionally targeted Ppargc1a allele.S5. Rapid dietary cross-over experiment of Fig 3.S6. scRNAseq analysis of Bmi1+ derived cells.S7. Inflammatory response to NWD1.
Figure S4 from Dynamic Intestinal Stem Cell Plasticity and Lineage Remodeling by a Nutritional Environment Relevant to Human Risk for Tumorigenesis
Authors: Choi Jiahn , Zhang Xusheng , Li Wenge , Houston Michele , Peregrina Karina , Dubin Robert , Ye Kenny , Augenlicht Leonard
Published: August 2023

Targeted knockout of Ppargc1a in Lgr5hi cells was confirmed, and trajectory analyses of dietary and genetic alterations confirmed by marker expression.
Supplementary Table 3 from ZEB1 Is Regulated by K811 Acetylation to Promote Stability, NuRD Complex Interactions, EMT, and NSCLC Metastasis
Authors: Perez-Oquendo Mabel , Manshouri Roxsan , Tian Yanhua , Fradette Jared J. , Rodriguez B. Leticia , Kundu Samrat T. , Gibbons Don L.
Published: August 2023

Antibody information
Supplementary Table 1 from ZEB1 Is Regulated by K811 Acetylation to Promote Stability, NuRD Complex Interactions, EMT, and NSCLC Metastasis
Authors: Perez-Oquendo Mabel , Manshouri Roxsan , Tian Yanhua , Fradette Jared J. , Rodriguez B. Leticia , Kundu Samrat T. , Gibbons Don L.
Published: August 2023

Tandem-mass spectrometry (MS/MS) analysis on ZEB1 uncovered five novel post-translational modification.
Figure S7 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

Comparing NE score-associated features between SCLC and other cancer types.
Figure S6 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

Examples of different and similar compound sensitivity dynamic ranges in SCLC and NBL.
Figure S4 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

SCLC vs. NBL concordance of NE score association with omics, drug sensitivity, and dependency data.
Figure S3 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

Controlling for MYCN amplification status increases the statistical significance of NE score vs. MYCN expression association.
Figure S2 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

Known NBL prognostic factors consistently associate with outcome across different NBL studies but not NE scores.
Figure 6 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

Similar and distinct NE score–associated therapeutic sensitivity in SCLC and neuroblastoma cell lines. A, Correlation between NE scores and therapeutic sensitivity for drugs with selected targets. Therapeutic sensitivity data were previously harmonized such that a higher value represents more resistance in each study. For each of the nine selected targets, all compounds with the same target were identified from multiple studies. Pearson correlation coefficient r from correlating compound data with NE scores were calculated for neuroblastoma lines (x-axis values) and SCLC lines (y-axis values), respectively and visualized as a scatter plot, with colors annotating the source of data, and transparency annotating the statistical significance. B, Meta-analysis–summarized correlation between drug therapeutic sensitivity and NE scores in neuroblastoma (x-axis) and SCLC (y-axis) cell lines. Note that high NE scores are associated with resistance to inhibitors of LCK, MEK, XIAP, mTOR, HSP90, and Abl, and sensitivity to BCL inhibitors. NE scores are associated with resistance to BRD inhibitors in neuroblastoma but not SCLC whereas microtubule inhibitors resistance correlates with high NE scores in SCLC but not neuroblastoma cell lines.
Figure 1 from A Comparative Study of Neuroendocrine Heterogeneity in Small Cell Lung Cancer and Neuroblastoma
Authors: Cai Ling , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua
Published: August 2023

The molecular similarity between neuroblastoma and SCLC. A, SCLC NE signature gene expression across different cancer lineages. The expression of NE (left half) and non-NE (right half) genes were averaged by cancer lineages and plotted as a heat map. The number of cell lines per lineage are visualized as bars plotted right to the heat map. Note that SCLC and neuroblastoma are the two cancer types with the highest number of cell lines in the cluster with high expression of NE genes. B–H, Hierarchical clustering of cell lines by omics and functional screening datasets. The number of cell lines and number of features used for clustering are as follows: 1,165 cell lines by expression of 19,159 genes (B), 897 lines by 214 RPPA features (C), 926 lines by 225 metabolites (D), 688 lines by CRISPR effect score of 509 genes (E), 648 lines by RNAi effect score of 375 genes (F), 624 lines by 208 compounds from GDSC (G), and 794 lines by 168 compounds from CTRP (H). Note the clustering for RNA-seq data was based on the top 10 principal components, RPPA and metabolomics clusterings were based on all available features; dependency and drug clusterings were based on selected consistent features as previously summarized. Each leaf on the dendrogram represents a cell line. The inner rim right outside the dendrogram signifies the cancer lineage and the outer rim indicates the NE score of the cell line.
Supplementary Figure 1 from Critical Role of 6-Phosphogluconate Dehydrogenase in TAp73-Mediated Cancer Cell Proliferation
Authors: Qiao Rui , Wei Mengmeng , Chen Hui , Zhang Xianhong , Zhang Jie , Gao Liyang , Ma Haijun , Wang Yujiong , Li Le
Published: August 2023

S1. TAp73 activates the expression of 6PGD
Data from MDM2 Inhibition Enhances Immune Checkpoint Inhibitor Efficacy by Increasing IL15 and MHC Class II Production
Authors: Langenbach Marlene , Giesler Sophie , Richtsfeld Stefan , Costa-Pereira Sara , Rindlisbacher Lukas , Wertheimer Tobias , Braun Lukas M. , Andrieux Geoffroy , Duquesne Sandra , Pfeifer Dietmar , Woessner Nadine M. , Menssen Hans D. , Taromi Sanaz , Duyster Justus , Börries Melanie , Brummer Tilman , Blazar Bruce R. , Minguet Susana , Turko Patrick , Levesque Mitchell P. , Becher Burkhard , Zeiser Robert
Published: August 2023

Abstract
The treatment of patients with metastatic melanoma with immune checkpoint inhibitors (ICI) leads to impressive response rates but primary and secondary resistance to ICI reduces progression-free survival. Novel strategies that interfere with resistance mechanisms are key to further improve patient outcome during ICI therapy. P53 is often inactivated by mouse-double-minute-2 (MDM2), which may decrease immunogenicity of melanoma cells. We analyzed primary patient-derived melanoma cell lines, performed bulk sequencing analysis of patient-derived melanoma samples, and used melanoma mouse models to investigate the role of MDM2-inhibition for enhanced ICI therapy. We found increased expression of IL15 and MHC-II in murine melanoma cells upon p53 induction by MDM2-inhibition. MDM2-inhibitor induced MHC-II and IL15-production, which was p53 dependent as Tp53 knockdown blocked the effect. Lack of IL15-receptor in hematopoietic cells or IL15 neutralization reduced the MDM2-inhibition/p53-induction–mediated antitumor immunity. P53 induction by MDM2-inhibition caused anti-melanoma immune memory as T cells isolated from MDM2-inhibitor–treated melanoma-bearing mice exhibited anti-melanoma activity in secondary melanoma-bearing mice. In patient-derived melanoma cells p53 induction by MDM2-inhibition increased IL15 and MHC-II. IL15 and CIITA expressions were associated with a more favorable prognosis in patients bearing WT but not TP53-mutated melanoma.
Implications:
MDM2-inhibition represents a novel strategy to enhance IL15 and MHC-II–production, which disrupts the immunosuppressive tumor microenvironment. On the basis of our findings, a clinical trial combining MDM2-inhibition with anti–PD-1 immunotherapy for metastatic melanoma is planned.
Supplementary Figure S3 from Progressive Spreading of DNA Methylation in the GSTP1 Promoter CpG Island across Transitions from Precursors to Invasive Prostate Cancer
Authors: Gupta Harshath , Inoue Hitoshi , Nakai Yasutomo , Nakayama Masashi , Jones Tracy , Hicks Jessica L. , Kumar Balasubramanian , Gurel Meltem , Nelson William G. , De Marzo Angelo M. , Yegnasubramanian Srinivasan
Published: August 2023

Supplementary Figure S3 shows the GSTP1 promoter methylation and its corresponding GSTP1 immunohistochemistry expression for PIA and PIN lesions within an individual patient, and notably the heterogeneity of the PIA lesions.
Supplementary Table 3 from Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan (GTX-CI) as First-line Treatment for Metastatic Pancreatic Cancer
Authors: Wilbur H. Catherine , Durham Jennifer N , Lim Su Jin , Purtell Katrina , Bever Katherine M. , Laheru Daniel A. , De Jesus-Acosta Ana , Azad Nilofer S. , Wilt Bradley , Diaz Luis A. , Le Dung T. , Wang Hao
Published: August 2023

Supplementary Table 3: Patient Characteristics
Supplementary Table 1 from Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan (GTX-CI) as First-line Treatment for Metastatic Pancreatic Cancer
Authors: Wilbur H. Catherine , Durham Jennifer N , Lim Su Jin , Purtell Katrina , Bever Katherine M. , Laheru Daniel A. , De Jesus-Acosta Ana , Azad Nilofer S. , Wilt Bradley , Diaz Luis A. , Le Dung T. , Wang Hao
Published: August 2023

Supplementary Table 1: Representativeness
Supplementary Figure 2 from Gemcitabine, Docetaxel, Capecitabine, Cisplatin, Irinotecan (GTX-CI) as First-line Treatment for Metastatic Pancreatic Cancer
Authors: Wilbur H. Catherine , Durham Jennifer N , Lim Su Jin , Purtell Katrina , Bever Katherine M. , Laheru Daniel A. , De Jesus-Acosta Ana , Azad Nilofer S. , Wilt Bradley , Diaz Luis A. , Le Dung T. , Wang Hao
Published: August 2023

Supplementary Figure 2: OS and PFS
Supplementary Table S2 from Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y. , Song Yingjie , Sesterhenn Isabell A. , Chesnut Gregory T. , Tan Shyh-Han
Published: August 2023

Supplementary Table S2 shows gene expression evaluated as a continuous variable and by median and Youden index cutoffs for BCR-free and metastasis-free survival.
Supplementary Figure S8 from Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y. , Song Yingjie , Sesterhenn Isabell A. , Chesnut Gregory T. , Tan Shyh-Han
Published: August 2023

Supplementary Figure S8 shows non-significant relative cell type scores by Dx Age Group.
Supplementary Figure S2 from Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y. , Song Yingjie , Sesterhenn Isabell A. , Chesnut Gregory T. , Tan Shyh-Han
Published: August 2023

Supplementary Figure S2 shows non-significant relative cell type scores by race.
Supplementary Figure S12 from Immunologic Assessment of Tumors from a Race-matched Military Cohort Identifies Mast Cell Depletion as a Marker of Prostate Cancer Progression
Authors: Schafer Cara C. , Jiang Jiji , Elsamanoudi Sally , Nousome Darryl , Young Denise Y. , Song Yingjie , Sesterhenn Isabell A. , Chesnut Gregory T. , Tan Shyh-Han
Published: August 2023

Supplementary Figure S12 shows Mast vs TILs scores plotted by race for Gleason Sum, GG, and Dx Age.