bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary figures from Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins
Authors: Zhang Maomao , Di Martino Julie S. , Bowman Robert L. , Campbell Nathaniel R. , Baksh Sanjeethan C. , Simon-Vermot Theresa , Kim Isabella S. , Haldeman Pearce , Mondal Chandrani , Yong-Gonzales Vladimir , Abu-Akeel Mohsen , Merghoub Taha , Jones Drew R. , Zhu Xiphias Ge , Arora Arshi , Ariyan Charlotte E. , Birsoy Kivanç , Wolchok Jedd D. , Panageas Katherine S. , Hollmann Travis , Bravo-Cordero Jose Javier , White Richard M.
Published: April 2023

Supplementary Figure S1: RNA-seq analysis of human A375 melanoma cells in co-culture with adipocytes compared to monoculture controls Supplementary Figure S2: Lipid transfer and melanoma cell uptake of long chain fatty acids Supplementary Figure S3: Adipocytes do not increase glycolysis in melanoma cells Supplementary Figure S4: Endogenous FATP expression in control tissues and patient-derived xenografts Supplementary Figure S5: Absence of lipid-laden tumor cells in in vivo setting devoid of adipocytes Supplementary Figure S6: Lipidomics reveals specific lipid species transferred from adipocytes to melanoma cells Supplementary Figure S7: FATP1 expression and survival Supplementary Figure S8: Validation of FATP1 knockdown Supplementary Figure S9: Lipofermata targets FATP1 Supplementary Figure S10: Compounds that are structurally similar to Lipofermata do not cause decreases in lipid uptake or increased cell death Supplementary Figure S11: Measurement of apoptosis in Lipofermata-treated cells
Supplemental Table 3 from Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins
Authors: Zhang Maomao , Di Martino Julie S. , Bowman Robert L. , Campbell Nathaniel R. , Baksh Sanjeethan C. , Simon-Vermot Theresa , Kim Isabella S. , Haldeman Pearce , Mondal Chandrani , Yong-Gonzales Vladimir , Abu-Akeel Mohsen , Merghoub Taha , Jones Drew R. , Zhu Xiphias Ge , Arora Arshi , Ariyan Charlotte E. , Birsoy Kivanç , Wolchok Jedd D. , Panageas Katherine S. , Hollmann Travis , Bravo-Cordero Jose Javier , White Richard M.
Published: April 2023

ZMEL in vitro lipidomics
Supplemental Table 2 from Adipocyte-Derived Lipids Mediate Melanoma Progression via FATP Proteins
Authors: Zhang Maomao , Di Martino Julie S. , Bowman Robert L. , Campbell Nathaniel R. , Baksh Sanjeethan C. , Simon-Vermot Theresa , Kim Isabella S. , Haldeman Pearce , Mondal Chandrani , Yong-Gonzales Vladimir , Abu-Akeel Mohsen , Merghoub Taha , Jones Drew R. , Zhu Xiphias Ge , Arora Arshi , Ariyan Charlotte E. , Birsoy Kivanç , Wolchok Jedd D. , Panageas Katherine S. , Hollmann Travis , Bravo-Cordero Jose Javier , White Richard M.
Published: April 2023

ZMEL RNAseq table S2
Supplemental Data File from Targeted Therapies for Targeted Populations: Anti-EGFR Treatment for EGFR-Amplified Gastroesophageal Adenocarcinoma
Authors: Maron Steven B. , Alpert Lindsay , Kwak Heewon A. , Lomnicki Samantha , Chase Leah , Xu David , O'Day Emily , Nagy Rebecca J. , Lanman Richard B. , Cecchi Fabiola , Hembrough Todd , Schrock Alexa , Hart John , Xiao Shu-Yuan , Setia Namrata , Catenacci Daniel V.T.
Published: April 2023

Detailed patient information who were treated with anti-EGFR therapy
Table S3 from Suppression of STING Associated with LKB1 Loss in KRAS-Driven Lung Cancer
Authors: Kitajima Shunsuke , Ivanova Elena , Guo Sujuan , Yoshida Ryohei , Campisi Marco , Sundararaman Shriram K. , Tange Shoichiro , Mitsuishi Yoichiro , Thai Tran C. , Masuda Sayuri , Piel Brandon P. , Sholl Lynette M. , Kirschmeier Paul T. , Paweletz Cloud P. , Watanabe Hideo , Yajima Mamiko , Barbie David A.
Published: April 2023

Table S3 shows list of KRAS WT; LKB1 WT and KRAS WT; LKB1 Mut lung adenocarcinoma cell lines related with supplementary figure S1.
Supplementary Figures from Sequential ALK Inhibitors Can Select for Lorlatinib-Resistant Compound ALK Mutations in ALK-Positive Lung Cancer
Authors: Yoda Satoshi , Lin Jessica J. , Lawrence Michael S. , Burke Benjamin J. , Friboulet Luc , Langenbucher Adam , Dardaei Leila , Prutisto-Chang Kylie , Dagogo-Jack Ibiayi , Timofeevski Sergei , Hubbeling Harper , Gainor Justin F. , Ferris Lorin A. , Riley Amanda K. , Kattermann Krystina E. , Timonina Daria , Heist Rebecca S. , Iafrate A. John , Benes Cyril H. , Lennerz Jochen K. , Mino-Kenudson Mari , Engelman Jeffrey A. , Johnson Ted W. , Hata Aaron N. , Shaw Alice T.
Published: April 2023

Supplementary Figures include Figure S1-S9.
Supplementary Figures and Table legends from Suppression of STING Associated with LKB1 Loss in KRAS-Driven Lung Cancer
Authors: Kitajima Shunsuke , Ivanova Elena , Guo Sujuan , Yoshida Ryohei , Campisi Marco , Sundararaman Shriram K. , Tange Shoichiro , Mitsuishi Yoichiro , Thai Tran C. , Masuda Sayuri , Piel Brandon P. , Sholl Lynette M. , Kirschmeier Paul T. , Paweletz Cloud P. , Watanabe Hideo , Yajima Mamiko , Barbie David A.
Published: April 2023

The supplementary file shows Supplementary figure S1-S4 and their legends, and the legends for Supplementary table S1-S4.
Supplementary Figure Legends from Impaired HLA Class I Antigen Processing and Presentation as a Mechanism of Acquired Resistance to Immune Checkpoint Inhibitors in Lung Cancer
Authors: Gettinger Scott , Choi Jungmin , Hastings Katherine , Truini Anna , Datar Ila , Sowell Ryan , Wurtz Anna , Dong Weilai , Cai Guoping , Melnick Mary Ann , Du Victor Y. , Schlessinger Joseph , Goldberg Sarah B. , Chiang Anne , Sanmamed Miguel F. , Melero Ignacio , Agorreta Jackeline , Montuenga Luis M. , Lifton Richard , Ferrone Soldano , Kavathas Paula , Rimm David L. , Kaech Susan M. , Schalper Kurt , Herbst Roy S. , Politi Katerina
Published: April 2023

Legends for Figures S1-S8
Supplementary Table S2 from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
Authors: Aguirre Andrew J. , Nowak Jonathan A. , Camarda Nicholas D. , Moffitt Richard A. , Ghazani Arezou A. , Hazar-Rethinam Mehlika , Raghavan Srivatsan , Kim Jaegil , Brais Lauren K. , Ragon Dorisanne , Welch Marisa W. , Reilly Emma , McCabe Devin , Marini Lori , Anderka Kristin , Helvie Karla , Oliver Nelly , Babic Ana , Da Silva Annacarolina , Nadres Brandon , Van Seventer Emily E. , Shahzade Heather A. , St. Pierre Joseph P. , Burke Kelly P. , Clancy Thomas , Cleary James M. , Doyle Leona A. , Jajoo Kunal , McCleary Nadine J. , Meyerhardt Jeffrey A. , Murphy Janet E. , Ng Kimmie , Patel Anuj K. , Perez Kimberly , Rosenthal Michael H. , Rubinson Douglas A. , Ryou Marvin , Shapiro Geoffrey I. , Sicinska Ewa , Silverman Stuart G. , Nagy Rebecca J. , Lanman Richard B. , Knoerzer Deborah , Welsch Dean J. , Yurgelun Matthew B. , Fuchs Charles S. , Garraway Levi A. , Getz Gad , Hornick Jason L. , Johnson Bruce E. , Kulke Matthew H. , Mayer Robert J. , Miller Jeffrey W. , Shyn Paul B. , Tuveson David A. , Wagle Nikhil , Yeh Jen Jen , Hahn William C. , Corcoran Ryan B. , Carter Scott L. , Wolpin Brian M.
Published: April 2023

Characteristics of biopsies obtained on PancSeq protocol.
Supplementary Table S1 from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
Authors: Aguirre Andrew J. , Nowak Jonathan A. , Camarda Nicholas D. , Moffitt Richard A. , Ghazani Arezou A. , Hazar-Rethinam Mehlika , Raghavan Srivatsan , Kim Jaegil , Brais Lauren K. , Ragon Dorisanne , Welch Marisa W. , Reilly Emma , McCabe Devin , Marini Lori , Anderka Kristin , Helvie Karla , Oliver Nelly , Babic Ana , Da Silva Annacarolina , Nadres Brandon , Van Seventer Emily E. , Shahzade Heather A. , St. Pierre Joseph P. , Burke Kelly P. , Clancy Thomas , Cleary James M. , Doyle Leona A. , Jajoo Kunal , McCleary Nadine J. , Meyerhardt Jeffrey A. , Murphy Janet E. , Ng Kimmie , Patel Anuj K. , Perez Kimberly , Rosenthal Michael H. , Rubinson Douglas A. , Ryou Marvin , Shapiro Geoffrey I. , Sicinska Ewa , Silverman Stuart G. , Nagy Rebecca J. , Lanman Richard B. , Knoerzer Deborah , Welsch Dean J. , Yurgelun Matthew B. , Fuchs Charles S. , Garraway Levi A. , Getz Gad , Hornick Jason L. , Johnson Bruce E. , Kulke Matthew H. , Mayer Robert J. , Miller Jeffrey W. , Shyn Paul B. , Tuveson David A. , Wagle Nikhil , Yeh Jen Jen , Hahn William C. , Corcoran Ryan B. , Carter Scott L. , Wolpin Brian M.
Published: April 2023

Characteristics of patients enrolled to PancSeq protocol
Supplementary Figures from Real-time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine
Authors: Aguirre Andrew J. , Nowak Jonathan A. , Camarda Nicholas D. , Moffitt Richard A. , Ghazani Arezou A. , Hazar-Rethinam Mehlika , Raghavan Srivatsan , Kim Jaegil , Brais Lauren K. , Ragon Dorisanne , Welch Marisa W. , Reilly Emma , McCabe Devin , Marini Lori , Anderka Kristin , Helvie Karla , Oliver Nelly , Babic Ana , Da Silva Annacarolina , Nadres Brandon , Van Seventer Emily E. , Shahzade Heather A. , St. Pierre Joseph P. , Burke Kelly P. , Clancy Thomas , Cleary James M. , Doyle Leona A. , Jajoo Kunal , McCleary Nadine J. , Meyerhardt Jeffrey A. , Murphy Janet E. , Ng Kimmie , Patel Anuj K. , Perez Kimberly , Rosenthal Michael H. , Rubinson Douglas A. , Ryou Marvin , Shapiro Geoffrey I. , Sicinska Ewa , Silverman Stuart G. , Nagy Rebecca J. , Lanman Richard B. , Knoerzer Deborah , Welsch Dean J. , Yurgelun Matthew B. , Fuchs Charles S. , Garraway Levi A. , Getz Gad , Hornick Jason L. , Johnson Bruce E. , Kulke Matthew H. , Mayer Robert J. , Miller Jeffrey W. , Shyn Paul B. , Tuveson David A. , Wagle Nikhil , Yeh Jen Jen , Hahn William C. , Corcoran Ryan B. , Carter Scott L. , Wolpin Brian M.
Published: April 2023

Supplementary Figure S1: Overview of workflow and data generation. Supplementary Figure S2: Analysis of neoplastic cellularity. Supplementary Figure S3: Recurrent copy number alterations. Supplementary Figure S4: Mutational signature analysis. Supplementary Figure S5: Analysis of PDAC gene expression signatures. Supplementary Figure S6: Clinically relevant alterations in the cohort.
Table S2 from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Authors: Rajbhandari Presha , Lopez Gonzalo , Capdevila Claudia , Salvatori Beatrice , Yu Jiyang , Rodriguez-Barrueco Ruth , Martinez Daniel , Yarmarkovich Mark , Weichert-Leahey Nina , Abraham Brian J. , Alvarez Mariano J. , Iyer Archana , Harenza Jo Lynne , Oldridge Derek , De Preter Katleen , Koster Jan , Asgharzadeh Shahab , Seeger Robert C. , Wei Jun S. , Khan Javed , Vandesompele Jo , Mestdagh Pieter , Versteeg Rogier , Look A. Thomas , Young Richard A. , Iavarone Antonio , Lasorella Anna , Silva Jose M. , Maris John M. , Califano Andrea
Published: April 2023

Differential expression and biological pathway enrichment analysis of neuroblastoma molecular subtypes
Table S1 from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Authors: Rajbhandari Presha , Lopez Gonzalo , Capdevila Claudia , Salvatori Beatrice , Yu Jiyang , Rodriguez-Barrueco Ruth , Martinez Daniel , Yarmarkovich Mark , Weichert-Leahey Nina , Abraham Brian J. , Alvarez Mariano J. , Iyer Archana , Harenza Jo Lynne , Oldridge Derek , De Preter Katleen , Koster Jan , Asgharzadeh Shahab , Seeger Robert C. , Wei Jun S. , Khan Javed , Vandesompele Jo , Mestdagh Pieter , Versteeg Rogier , Look A. Thomas , Young Richard A. , Iavarone Antonio , Lasorella Anna , Silva Jose M. , Maris John M. , Califano Andrea
Published: April 2023

Neuroblastoma Molecular subtypes and clinical information.
Supplementary Data from Cross-Cohort Analysis Identifies a TEAD4–MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma
Authors: Rajbhandari Presha , Lopez Gonzalo , Capdevila Claudia , Salvatori Beatrice , Yu Jiyang , Rodriguez-Barrueco Ruth , Martinez Daniel , Yarmarkovich Mark , Weichert-Leahey Nina , Abraham Brian J. , Alvarez Mariano J. , Iyer Archana , Harenza Jo Lynne , Oldridge Derek , De Preter Katleen , Koster Jan , Asgharzadeh Shahab , Seeger Robert C. , Wei Jun S. , Khan Javed , Vandesompele Jo , Mestdagh Pieter , Versteeg Rogier , Look A. Thomas , Young Richard A. , Iavarone Antonio , Lasorella Anna , Silva Jose M. , Maris John M. , Califano Andrea
Published: April 2023

Supplementary Experimental Procedures; Supplementary Figures S1-S10; Supplementary Table Legends S1-S9; Supplementary Tables S8-S9; Additional References
Figures S1-S8 from BRCA Reversion Mutations in Circulating Tumor DNA Predict Primary and Acquired Resistance to the PARP Inhibitor Rucaparib in High-Grade Ovarian Carcinoma
Authors: Lin Kevin K. , Harrell Maria I. , Oza Amit M. , Oaknin Ana , Ray-Coquard Isabelle , Tinker Anna V. , Helman Elena , Radke Marc R. , Say Carmen , Vo Lan-Thanh , Mann Elaina , Isaacson Jeffrey D. , Maloney Lara , O'Malley David M. , Chambers Setsuko K. , Kaufmann Scott H. , Scott Clare L. , Konecny Gottfried E. , Coleman Robert L. , Sun James X. , Giordano Heidi , Brenton James D. , Harding Thomas C. , McNeish Iain A. , Swisher Elizabeth M.
Published: April 2023

Figure S1 shows a consort diagram of patients with pretreatment and postprogression circulating cell-free DNA samples sequenced; Figure S2 shows a bar graph showing that a significantly lower level of the serum marker CA-125 was found at study enrollment in patients with no TP53 or BRCA mutations detected in the pretreatment circulating cell-free DNA; Figure S3 shows a scatter plot showing significant correlation between mutant allele frequency of primary somatic BRCA and TP53 mutations detected in pretreatment circulating cell-free DNA; Figure S4 shows a graph indicating the location of deleterious BRCA mutations where reversion mutations were detected in pretreatment and postprogression circulating cell-free DNA; Figure S5 shows a scatter plot showing a significant correlation of mutation allele frequency for the detected primary deleterious BRCA mutations between two independent next-generation sequencing-based circulating cell-free DNA assays; Figure S6 shows a swimlane graph showing the duration on rucaparib treatment of patients with or without BRCA reversion mutations detected in pretreatment circulating cell-free DNA; Figure S7 shows a graph from a linear regression analysis between the sum of mutation allele frequency of BRCA reversion mutations from pretreatment plasma and rucaparib progression-free survival; Figure S8 shows a bar graph of changes in BRCA reversion allele frequencies detected in pretreatment and postprogression circulating cell-free DNA from one patient.
Supplementary Table S5 from Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs
Authors: Dobson Stephanie M. , García-Prat Laura , Vanner Robert J. , Wintersinger Jeffrey , Waanders Esmé , Gu Zhaohui , McLeod Jessica , Gan Olga I. , Grandal Ildiko , Payne-Turner Debbie , Edmonson Michael N. , Ma Xiaotu , Fan Yiping , Voisin Veronique , Chan-Seng-Yue Michelle , Xie Stephanie Z. , Hosseini Mohsen , Abelson Sagi , Gupta Pankaj , Rusch Michael , Shao Ying , Olsen Scott R. , Neale Geoffrey , Chan Steven M. , Bader Gary , Easton John , Guidos Cynthia J. , Danska Jayne S. , Zhang Jinghui , Minden Mark D. , Morris Quaid , Mullighan Charles G. , Dick John E.
Published: April 2023

PDX targeted-sequencing tissue concordance
Supplementary Table S2 from Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs
Authors: Dobson Stephanie M. , García-Prat Laura , Vanner Robert J. , Wintersinger Jeffrey , Waanders Esmé , Gu Zhaohui , McLeod Jessica , Gan Olga I. , Grandal Ildiko , Payne-Turner Debbie , Edmonson Michael N. , Ma Xiaotu , Fan Yiping , Voisin Veronique , Chan-Seng-Yue Michelle , Xie Stephanie Z. , Hosseini Mohsen , Abelson Sagi , Gupta Pankaj , Rusch Michael , Shao Ying , Olsen Scott R. , Neale Geoffrey , Chan Steven M. , Bader Gary , Easton John , Guidos Cynthia J. , Danska Jayne S. , Zhang Jinghui , Minden Mark D. , Morris Quaid , Mullighan Charles G. , Dick John E.
Published: April 2023

Leukemia-initiating cell frequencies of paired diagnosis and relapse patient samples
Supplementary Table S1 from Relapse-Fated Latent Diagnosis Subclones in Acute B Lineage Leukemia Are Drug Tolerant and Possess Distinct Metabolic Programs
Authors: Dobson Stephanie M. , García-Prat Laura , Vanner Robert J. , Wintersinger Jeffrey , Waanders Esmé , Gu Zhaohui , McLeod Jessica , Gan Olga I. , Grandal Ildiko , Payne-Turner Debbie , Edmonson Michael N. , Ma Xiaotu , Fan Yiping , Voisin Veronique , Chan-Seng-Yue Michelle , Xie Stephanie Z. , Hosseini Mohsen , Abelson Sagi , Gupta Pankaj , Rusch Michael , Shao Ying , Olsen Scott R. , Neale Geoffrey , Chan Steven M. , Bader Gary , Easton John , Guidos Cynthia J. , Danska Jayne S. , Zhang Jinghui , Minden Mark D. , Morris Quaid , Mullighan Charles G. , Dick John E.
Published: April 2023

Patient characteristics and patient genomic analysis (WES and SNP 6.0)
Tables S1-S8 from The Evolutionary Origins of Recurrent Pancreatic Cancer
Authors: Sakamoto Hitomi , Attiyeh Marc A. , Gerold Jeffrey M. , Makohon-Moore Alvin P. , Hayashi Akimasa , Hong Jungeui , Kappagantula Rajya , Zhang Lance , Melchor Jerry P. , Reiter Johannes G. , Heyde Alexander , Bielski Craig M. , Penson Alexander V. , Gönen Mithat , Chakravarty Debyani , O'Reilly Eileen M. , Wood Laura D. , Hruban Ralph H. , Nowak Martin A. , Socci Nicholas D. , Taylor Barry S. , Iacobuzio-Donahue Christine A.
Published: April 2023

Supplemental Tables
Supplementary Data from Disabled Homolog 2 Controls Prometastatic Activity of Tumor-Associated Macrophages
Authors: Marigo Ilaria , Trovato Rosalinda , Hofer Francesca , Ingangi Vincenzo , De Sanctis Francesco , Ugel Stefano , Canè Stefania , Simonelli Anna , Lamolinara Alessia , Iezzi Manuela , Fassan Matteo , Rugge Massimo , Boschi Federico , Borile Giulia , Eisenhaure Thomas , Sarkizova Siranush , Lieb David , Hacohen Nir , Azzolin Luca , Piccolo Stefano , Lawlor Rita , Scarpa Aldo , Carbognin Luisa , Bria Emilio , Bicciato Silvio , Murray Peter J. , Bronte Vincenzo
Published: April 2023

Supplementary Figures, Tables, Methods
Supplementary Table S6 from An In Vivo Kras Allelic Series Reveals Distinct Phenotypes of Common Oncogenic Variants
Authors: Zafra Maria Paz , Parsons Marie J. , Kim Jangkyung , Alonso-Curbelo Direna , Goswami Sukanya , Schatoff Emma M. , Han Teng , Katti Alyna , Fernandez Maria Teresa Calvo , Wilkinson John E. , Piskounova Elena , Dow Lukas E.
Published: April 2023

oligonucleotide sequences
Supplementary Table S5 from An In Vivo Kras Allelic Series Reveals Distinct Phenotypes of Common Oncogenic Variants
Authors: Zafra Maria Paz , Parsons Marie J. , Kim Jangkyung , Alonso-Curbelo Direna , Goswami Sukanya , Schatoff Emma M. , Han Teng , Katti Alyna , Fernandez Maria Teresa Calvo , Wilkinson John E. , Piskounova Elena , Dow Lukas E.
Published: April 2023

Differential gene expression analysis of RNAseq from organoids
Tables S1-S4 from Priority COVID-19 Vaccination for Patients with Cancer while Vaccine Supply Is Limited
Authors: Ribas Antoni , Sengupta Rajarshi , Locke Trevan , Zaidi Sayyed Kaleem , Campbell Katie M. , Carethers John M. , Jaffee Elizabeth M. , Wherry E. John , Soria Jean-Charles , D'Souza Gypsyamber
Published: April 2023

Supplemental Table S1. Studies comparing outcomes among SARS-COV-2 infected patients with cancer and those without cancer. Supplemental Table S2. Studies comparing outcomes among SARS-COV-2 infected patients with cancer and uninfected patients with cancer Supplemental Table S3. Studies reporting outcomes among SARS-COV-2 infected patients with cancer without any comparison Supplemental Table S4. Metanalyses of published studies on COVID-19-cancer connection
AACR COVID-19 and Cancer Task Force Bios from Priority COVID-19 Vaccination for Patients with Cancer while Vaccine Supply Is Limited
Authors: Ribas Antoni , Sengupta Rajarshi , Locke Trevan , Zaidi Sayyed Kaleem , Campbell Katie M. , Carethers John M. , Jaffee Elizabeth M. , Wherry E. John , Soria Jean-Charles , D'Souza Gypsyamber
Published: April 2023

AACR COVID-19 and Cancer Task Force Bios
Supplementary Figures and Legends from EZH2-Deficient T-cell Acute Lymphoblastic Leukemia Is Sensitized to CHK1 Inhibition through Enhanced Replication Stress
Authors: León Theresa E. , Rapoz-D'Silva Tanya , Bertoli Cosetta , Rahman Sunniyat , Magnussen Michael , Philip Brian , Farah Nadine , Richardson Simon E. , Ahrabi Sara , Guerra-Assunção José Afonso , Gupta Rajeev , Nacheva Elisabeth P. , Henderson Stephen , Herrero Javier , Linch David C. , de Bruin Robertus A.M. , Mansour Marc R.
Published: April 2023

Supplementary Figures and Legends
Supplemental Table 4 from The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor–Positive Metastatic Breast Cancer
Authors: Wander Seth A. , Cohen Ofir , Gong Xueqian , Johnson Gabriela N. , Buendia-Buendia Jorge E. , Lloyd Maxwell R. , Kim Dewey , Luo Flora , Mao Pingping , Helvie Karla , Kowalski Kailey J. , Nayar Utthara , Waks Adrienne G. , Parsons Stephen H. , Martinez Ricardo , Litchfield Lacey M. , Ye Xiang S. , Yu Chunping , Jansen Valerie M. , Stille John R. , Smith Patricia S. , Oakley Gerard J. , Chu Quincy S. , Batist Gerald , Hughes Melissa E. , Kremer Jill D. , Garraway Levi A. , Winer Eric P. , Tolaney Sara M. , Lin Nancy U. , Buchanan Sean G. , Wagle Nikhil
Published: April 2023

Supplemental Table 4
Supplementary Table 2 from Leukemia Cell of Origin Influences Apoptotic Priming and Sensitivity to LSD1 Inhibition
Authors: Cai Sheng F. , Chu S. Haihua , Goldberg Aaron D. , Parvin Salma , Koche Richard P. , Glass Jacob L. , Stein Eytan M. , Tallman Martin S. , Sen Filiz , Famulare Christopher A. , Cusan Monica , Huang Chun-Hao , Chen Chun-Wei , Zou Lihua , Cordner Keith B. , DelGaudio Nicole L. , Durani Vidushi , Kini Mitali , Rex Madison , Tian Helen S. , Zuber Johannes , Baslan Timour , Lowe Scott W. , Rienhoff Hugh Y. , Letai Anthony , Levine Ross L. , Armstrong Scott A.
Published: April 2023

Bliss synergy scores for in vitro venetoclax/IMG-7289 combination treatment
Supplementary Data from Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy
Authors: Driehuis Else , Kolders Sigrid , Spelier Sacha , Lõhmussaar Kadi , Willems Stefan M. , Devriese Lot A. , de Bree Remco , de Ruiter Emma J. , Korving Jeroen , Begthel Harry , van Es Johan H. , Geurts Veerle , He Gui-Wei , van Jaarsveld Richard H. , Oka Rurika , Muraro Mauro J. , Vivié Judith , Zandvliet Maurice M.J.M. , Hendrickx Antoni P.A. , Iakobachvili Nino , Sridevi Priya , Kranenburg Onno , van Boxtel Ruben , Kops Geert J.P.L. , Tuveson David A. , Peters Peter J. , van Oudenaarden Alexander , Clevers Hans
Published: April 2023

Supplementary Figures including legends, Supplementary Tables
Movie S5 from Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy
Authors: Driehuis Else , Kolders Sigrid , Spelier Sacha , Lõhmussaar Kadi , Willems Stefan M. , Devriese Lot A. , de Bree Remco , de Ruiter Emma J. , Korving Jeroen , Begthel Harry , van Es Johan H. , Geurts Veerle , He Gui-Wei , van Jaarsveld Richard H. , Oka Rurika , Muraro Mauro J. , Vivié Judith , Zandvliet Maurice M.J.M. , Hendrickx Antoni P.A. , Iakobachvili Nino , Sridevi Priya , Kranenburg Onno , van Boxtel Ruben , Kops Geert J.P.L. , Tuveson David A. , Peters Peter J. , van Oudenaarden Alexander , Clevers Hans
Published: April 2023

Movie S5 from Oral Mucosal Organoids as a Potential Platform for Personalized Cancer Therapy
Table S2 from Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways
Authors: Pham Trang H. , Hagenbeek Thijs J. , Lee Ho-June , Li Jason , Rose Christopher M. , Lin Eva , Yu Mamie , Martin Scott E. , Piskol Robert , Lacap Jennifer A. , Sampath Deepak , Pham Victoria C. , Modrusan Zora , Lill Jennie R. , Klijn Christiaan , Malek Shiva , Chang Matthew T. , Dey Anwesha
Published: April 2023

Cluster score correlation with YAP/TAZ dependency
Table S1 from Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways
Authors: Pham Trang H. , Hagenbeek Thijs J. , Lee Ho-June , Li Jason , Rose Christopher M. , Lin Eva , Yu Mamie , Martin Scott E. , Piskol Robert , Lacap Jennifer A. , Sampath Deepak , Pham Victoria C. , Modrusan Zora , Lill Jennie R. , Klijn Christiaan , Malek Shiva , Chang Matthew T. , Dey Anwesha
Published: April 2023

Summary table of cell lines and cluster attributes
Figure S4 from Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways
Authors: Pham Trang H. , Hagenbeek Thijs J. , Lee Ho-June , Li Jason , Rose Christopher M. , Lin Eva , Yu Mamie , Martin Scott E. , Piskol Robert , Lacap Jennifer A. , Sampath Deepak , Pham Victoria C. , Modrusan Zora , Lill Jennie R. , Klijn Christiaan , Malek Shiva , Chang Matthew T. , Dey Anwesha
Published: April 2023

Supplementary Figure 4
Figure S2 from Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways
Authors: Pham Trang H. , Hagenbeek Thijs J. , Lee Ho-June , Li Jason , Rose Christopher M. , Lin Eva , Yu Mamie , Martin Scott E. , Piskol Robert , Lacap Jennifer A. , Sampath Deepak , Pham Victoria C. , Modrusan Zora , Lill Jennie R. , Klijn Christiaan , Malek Shiva , Chang Matthew T. , Dey Anwesha
Published: April 2023

Supplementary Figure 2
Figure S1 from Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways
Authors: Pham Trang H. , Hagenbeek Thijs J. , Lee Ho-June , Li Jason , Rose Christopher M. , Lin Eva , Yu Mamie , Martin Scott E. , Piskol Robert , Lacap Jennifer A. , Sampath Deepak , Pham Victoria C. , Modrusan Zora , Lill Jennie R. , Klijn Christiaan , Malek Shiva , Chang Matthew T. , Dey Anwesha
Published: April 2023

Supplementary Figure 1
Table S1 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis
Authors: Hong Xin , Roh Whijae , Sullivan Ryan J. , Wong Keith H.K. , Wittner Ben S. , Guo Hongshan , Dubash Taronish D. , Sade-Feldman Moshe , Wesley Benjamin , Horwitz Elad , Boland Genevieve M. , Marvin Dieuwke L. , Bonesteel Todd , Lu Chenyue , Aguet François , Burr Risa , Freeman Samuel S. , Parida Laxmi , Calhoun Katherine , Jewett Michelle K. , Nieman Linda T. , Hacohen Nir , Näär Anders M. , Ting David T. , Toner Mehmet , Stott Shannon L. , Getz Gad , Maheswaran Shyamala , Haber Daniel A.
Published: April 2023

Table S1
Supplementary Data from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis
Authors: Hong Xin , Roh Whijae , Sullivan Ryan J. , Wong Keith H.K. , Wittner Ben S. , Guo Hongshan , Dubash Taronish D. , Sade-Feldman Moshe , Wesley Benjamin , Horwitz Elad , Boland Genevieve M. , Marvin Dieuwke L. , Bonesteel Todd , Lu Chenyue , Aguet François , Burr Risa , Freeman Samuel S. , Parida Laxmi , Calhoun Katherine , Jewett Michelle K. , Nieman Linda T. , Hacohen Nir , Näär Anders M. , Ting David T. , Toner Mehmet , Stott Shannon L. , Getz Gad , Maheswaran Shyamala , Haber Daniel A.
Published: April 2023

Supplementary Information
Supplementary Data from Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia
Authors: Bhatnagar Bhavana , Kohlschmidt Jessica , Mrózek Krzysztof , Zhao Qiuhong , Fisher James L. , Nicolet Deedra , Walker Christopher J. , Mims Alice S. , Oakes Christopher , Giacopelli Brian , Orwick Shelley , Boateng Isaiah , Blachly James S. , Maharry Sophia E. , Carroll Andrew J. , Powell Bayard L. , Kolitz Jonathan E. , Stone Richard M. , Byrd John C. , Paskett Electra D. , de la Chapelle Albert , Garzon Ramiro , Eisfeld Ann-Kathrin
Published: April 2023

Supplementary Figures and Tables
Supplementary Table S23 from Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Authors: Elyada Ela , Bolisetty Mohan , Laise Pasquale , Flynn William F. , Courtois Elise T. , Burkhart Richard A. , Teinor Jonathan A. , Belleau Pascal , Biffi Giulia , Lucito Matthew S. , Sivajothi Santhosh , Armstrong Todd D. , Engle Dannielle D. , Yu Kenneth H. , Hao Yuan , Wolfgang Christopher L. , Park Youngkyu , Preall Jonathan , Jaffee Elizabeth M. , Califano Andrea , Robson Paul , Tuveson David A.
Published: April 2023

Supplementary Table S23 shows GSEA of KPC mouse CAFs
Supplementary Table S22 from Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Authors: Elyada Ela , Bolisetty Mohan , Laise Pasquale , Flynn William F. , Courtois Elise T. , Burkhart Richard A. , Teinor Jonathan A. , Belleau Pascal , Biffi Giulia , Lucito Matthew S. , Sivajothi Santhosh , Armstrong Todd D. , Engle Dannielle D. , Yu Kenneth H. , Hao Yuan , Wolfgang Christopher L. , Park Youngkyu , Preall Jonathan , Jaffee Elizabeth M. , Califano Andrea , Robson Paul , Tuveson David A.
Published: April 2023

Supplementary Table S22 shows the marker genes of the different KPC fibroblasts sub-clusters
Supplementary Table S20 from Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Authors: Elyada Ela , Bolisetty Mohan , Laise Pasquale , Flynn William F. , Courtois Elise T. , Burkhart Richard A. , Teinor Jonathan A. , Belleau Pascal , Biffi Giulia , Lucito Matthew S. , Sivajothi Santhosh , Armstrong Todd D. , Engle Dannielle D. , Yu Kenneth H. , Hao Yuan , Wolfgang Christopher L. , Park Youngkyu , Preall Jonathan , Jaffee Elizabeth M. , Califano Andrea , Robson Paul , Tuveson David A.
Published: April 2023

Supplementary Table S20 shows the marker genes of the different clusters in the fibroblast-enriched KPC analysis
Supplementary Table S10 from Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Authors: Elyada Ela , Bolisetty Mohan , Laise Pasquale , Flynn William F. , Courtois Elise T. , Burkhart Richard A. , Teinor Jonathan A. , Belleau Pascal , Biffi Giulia , Lucito Matthew S. , Sivajothi Santhosh , Armstrong Todd D. , Engle Dannielle D. , Yu Kenneth H. , Hao Yuan , Wolfgang Christopher L. , Park Youngkyu , Preall Jonathan , Jaffee Elizabeth M. , Califano Andrea , Robson Paul , Tuveson David A.
Published: April 2023

Supplementary Table S10 shows marker genes of the different human T & NK cell sub-clusters
Table S1 from A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS–Driven Lung Cancer
Authors: Cai Hongchen , Chew Su Kit , Li Chuan , Tsai Min K. , Andrejka Laura , Murray Christopher W. , Hughes Nicholas W. , Shuldiner Emily G. , Ashkin Emily L. , Tang Rui , Hung King L. , Chen Leo C. , Lee Shi Ya C. , Yousefi Maryam , Lin Wen-Yang , Kunder Christian A. , Cong Le , McFarland Christopher D. , Petrov Dmitri A. , Swanton Charles , Winslow Monte M.
Published: April 2023

Table S1. Mutation data of the genes that we selected for investigation.
Supplementary Figure S12 from Resistance to Durvalumab and Durvalumab plus Tremelimumab Is Associated with Functional STK11 Mutations in Patients with Non–Small Cell Lung Cancer and Is Reversed by STAT3 Knockdown
Authors: Pore Nabendu , Wu Song , Standifer Nathan , Jure-Kunkel Maria , de los Reyes Melissa , Shrestha Yashaswi , Halpin Rebecca , Rothstein Raymond , Mulgrew Kathy , Blackmore Stephen , Martin Philip , Meekin John , Griffin Matthew , Bisha Ina , Proia Theresa A. , Miragaia Ricardo J. , Herbst Ronald , Gupta Ashok , Abdullah Shaad E. , Raja Rajiv , Frigault Melanie M. , Barrett J. Carl , Dennis Phillip A. , Ascierto Maria Libera , Oberst Michael D.
Published: April 2023

Pharmacodynamics of STAT3 ASO in CT26 STK11 KO model. (A) Percentage of CD45+ immune cells among live cells from untreated or drug-treated STK11 KO CT26 tumors as indicated. (B) Percentage of Ly6G+ granulocytic cells among live CD45+ cells. (C) Percentage of intratumoral CD103+ cDC1 dendritic cells among CD45+ immune cells. (D) CD86 MFI of CD103+ cDC1s. (E) Percentage of migratory DC among CD45+ cells in TDLN of tumor engrafted mice. (F) CD86 MFI of these migratory DC in TDLNs. (G) Flow cytometry plots of CD86 levels on TDLN migratory DC. (H) Percentage of CD64+ CD11b+ myeloid cells among live intratumoral CD45+ cells. (I) Flow cytometry plots of CD86 on these CD64+ CD11b+ myeloid cells. (J) Percentages of MHCII+ CD206+ intratumoral myeloid cells. (K) Percentage of MHCII+ CD163+ intratumoral myeloid cells.
Supplementary Data from INK4 Tumor Suppressor Proteins Mediate Resistance to CDK4/6 Kinase Inhibitors
Authors: Li Qing , Jiang Baishan , Guo Jiaye , Shao Hong , Del Priore Isabella S. , Chang Qing , Kudo Rei , Li Zhiqiang , Razavi Pedram , Liu Bo , Boghossian Andrew S. , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Donovan Katherine A. , Palafox Marta , Reis-Filho Jorge S. , de Stanchina Elisa , Fischer Eric S. , Rosen Neal , Serra Violeta , Koff Andrew , Chodera John D. , Gray Nathanael S. , Chandarlapaty Sarat
Published: April 2023

Supplementary Data from INK4 Tumor Suppressor Proteins Mediate Resistance to CDK4/6 Kinase Inhibitors
Data from TGF-β Signaling in Myeloid Cells Is Required for Tumor Metastasis
Authors: Pang Yanli , Gara Sudheer Kumar , Achyut Bhagelu R. , Li Zhaoyang , Yan Hannah H. , Day Chi-Ping , Weiss Jonathan M. , Trinchieri Giorgio , Morris John C. , Yang Li
Published: April 2023

Abstract
TGF-β is overexpressed in advanced human cancers. It correlates with metastasis and poor prognosis. However, TGF-β functions as both a tumor suppressor and a tumor promoter. Here, we report for the first time that genetic deletion of Tgfbr2 specifically in myeloid cells (Tgfbr2MyeKO) significantly inhibited tumor metastasis. Reconstitution of tumor-bearing mice with Tgfbr2MyeKO bone marrow recapitulated the inhibited metastasis phenotype. This effect is mediated through decreased production of type II cytokines, TGF-β1, arginase 1, and inducible nitric oxide synthase, which promoted IFN-γ production and improved systemic immunity. Depletion of CD8 T cells diminished the metastasis defect in the Tgfbr2MyeKO mice. Consistent with animal studies, myeloid cells from patients with advanced-stage cancer showed increased TGF-β receptor II expression. Our studies show that myeloid-specific TGF-β signaling is an essential component of the metastasis-promoting puzzle of TGF-β. This is in contrast to the previously reported tumor-suppressing phenotypes in fibroblasts, epithelial cells, and T cells.

Significance: Our study identifies myeloid-specific TGF-β signaling as a critical mediator in tumor metastasis, distinct from the tumor-suppressive effect of TGF-β signaling in epithelial cells, fibroblasts, and T cells. We further provide mechanistic insight into host antitumor immunity and suggest a cell type–specific cancer-targeting strategy. Cancer Discov; 3(8); 936–51. ©2013 AACR.

See related commentary by Souza-Fonseca-Guimaraes and Smyth, p. 846

This article is highlighted in the In This Issue feature, p. 826
Data from Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Authors: Ye Jiangbin , Fan Jing , Venneti Sriram , Wan Ying-Wooi , Pawel Bruce R. , Zhang Ji , Finley Lydia W.S. , Lu Chao , Lindsten Tullia , Cross Justin R. , Qing Guoliang , Liu Zhandong , Simon M. Celeste , Rabinowitz Joshua D. , Thompson Craig B.
Published: April 2023

Abstract
The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2), is induced when MYC-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+, resulting in net production of NADPH from NADP+. Knockdown of SHMT2 in MYC-dependent cells reduced cellular NADPH:NADP+ ratio, increased cellular reactive oxygen species, and triggered hypoxia-induced cell death. In vivo, SHMT2 suppression led to impaired tumor growth. In MYC-amplified neuroblastoma patient samples, there was a significant correlation between SHMT2 and hypoxia-inducible factor-1 α (HIF1α), and SHMT2 expression correlated with unfavorable patient prognosis. Together, these data demonstrate that mitochondrial serine catabolism supports tumor growth by maintaining mitochondrial redox balance and cell survival.

Significance: In this study, we demonstrate that the mitochondrial enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth. Cancer Discov; 4(12); 1406–17. ©2014 AACR.

See related commentary by Martínez-Reyes and Chandel, p. 1371

This article is highlighted in the In This Issue feature, p. 1355
Data from Epigenetic Switch–Induced Viral Mimicry Evasion in Chemotherapy-Resistant Breast Cancer
Authors: Deblois Geneviève , Tonekaboni Seyed Ali Madani , Grillo Giacomo , Martinez Constanza , Kao Yunchi Ingrid , Tai Felicia , Ettayebi Ilias , Fortier Anne-Marie , Savage Paul , Fedor Alexandra N. , Liu Xiaojing , Guilhamon Paul , Lima-Fernandes Evelyne , Murison Alex , Kuasne Hellen , Ba-alawi Wail , Cescon David W. , Arrowsmith Cheryl H. , De Carvalho Daniel D. , Haibe-Kains Benjamin , Locasale Jason W. , Park Morag , Lupien Mathieu
Published: April 2023

Abstract
Tumor progression upon treatment arises from preexisting resistant cancer cells and/or adaptation of persister cancer cells committing to an expansion phase. Here, we show that evasion from viral mimicry response allows the growth of taxane-resistant triple-negative breast cancer (TNBC). This is enabled by an epigenetic state adapted to taxane-induced metabolic stress, where DNA hypomethylation over loci enriched in transposable elements (TE) is compensated by large chromatin domains of H3K27me3 to warrant TE repression. This epigenetic state creates a vulnerability to epigenetic therapy against EZH2, the H3K27me3 methyltransferase, which alleviates TE repression in taxane-resistant TNBC, leading to double-stranded RNA production and growth inhibition through viral mimicry response. Collectively, our results illustrate how epigenetic states over TEs promote cancer progression under treatment and can inform about vulnerabilities to epigenetic therapy.
Significance:
Drug-resistant cancer cells represent a major barrier to remission for patients with cancer. Here we show that drug-induced metabolic perturbation and epigenetic states enable evasion from the viral mimicry response induced by chemotherapy in TNBC. These epigenetic states define a vulnerability to epigenetic therapy using EZH2 inhibitors in taxane-resistant TNBC.

See related commentary by Janin and Esteller, p. 1258.

This article is highlighted in the In This Issue feature, p. 1241
Data from Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade
Authors: Zhang Qu , Luo Jia , Wu Song , Si Han , Gao Chen , Xu Wenjing , Abdullah Shaad E. , Higgs Brandon W. , Dennis Phillip A. , van der Heijden Michiel S. , Segal Neil H. , Chaft Jamie E. , Hembrough Todd , Barrett J. Carl , Hellmann Matthew D.
Published: April 2023

Abstract
The utility of circulating tumor DNA (ctDNA) as a biomarker in patients with advanced cancers receiving immunotherapy is uncertain. We therefore analyzed pretreatment (n = 978) and on-treatment (n = 171) ctDNA samples across 16 advanced-stage tumor types from three phase I/II trials of durvalumab (± the anti-CTLA4 therapy tremelimumab). Higher pretreatment variant allele frequencies (VAF) were associated with poorer overall survival (OS) and other known prognostic factors, but not objective response, suggesting a prognostic role for patient outcomes. On-treatment reductions in VAF and lower on-treatment VAF were independently associated with longer progression-free survival and OS and increased objective response rate, but not prognostic variables, suggesting that on-treatment ctDNA dynamics are predictive of benefit from immune checkpoint blockade. Accordingly, we propose a concept of “molecular response” using ctDNA, incorporating both pretreatment and on-treatment VAF, that predicted long-term survival similarly to initial radiologic response while also permitting early differentiation of responders among patients with initially radiologically stable disease.
Significance:
In a pan-cancer analysis of immune checkpoint blockade, pretreatment ctDNA levels appeared prognostic and on-treatment dynamics predictive. A “molecular response” metric identified long-term responders and adjudicated benefit among patients with initially radiologically stable disease. Changes in ctDNA may be more dynamic than radiographic changes and could complement existing trial endpoints.

This article is highlighted in the In This Issue feature, p. 1775
Data from Regulatory T-cell Depletion Alters the Tumor Microenvironment and Accelerates Pancreatic Carcinogenesis
Authors: Zhang Yaqing , Lazarus Jenny , Steele Nina G. , Yan Wei , Lee Ho-Joon , Nwosu Zeribe C. , Halbrook Christopher J. , Menjivar Rosa E. , Kemp Samantha B. , Sirihorachai Veerin R. , Velez-Delgado Ashley , Donahue Katelyn , Carpenter Eileen S. , Brown Kristee L. , Irizarry-Negron Valerie , Nevison Anna C. , Vinta Alekya , Anderson Michelle A. , Crawford Howard C. , Lyssiotis Costas A. , Frankel Timothy L. , Bednar Filip , Pasca di Magliano Marina
Published: April 2023

Abstract
Regulatory T cells (Treg) are abundant in human and mouse pancreatic cancer. To understand the contribution to the immunosuppressive microenvironment, we depleted Tregs in a mouse model of pancreatic cancer. Contrary to our expectations, Treg depletion failed to relieve immunosuppression and led to accelerated tumor progression. We show that Tregs are a key source of TGFβ ligands and, accordingly, their depletion reprogramed the fibroblast population, with loss of tumor-restraining, smooth muscle actin–expressing fibroblasts. Conversely, we observed an increase in chemokines Ccl3, Ccl6, and Ccl8 leading to increased myeloid cell recruitment, restoration of immune suppression, and promotion of carcinogenesis, an effect that was inhibited by blockade of the common CCL3/6/8 receptor CCR1. Further, Treg depletion unleashed pathologic CD4+ T-cell responses. Our data point to new mechanisms regulating fibroblast differentiation in pancreatic cancer and support the notion that fibroblasts are a heterogeneous population with different and opposing functions in pancreatic carcinogenesis.
Significance:
Here, we describe an unexpected cross-talk between Tregs and fibroblasts in pancreatic cancer. Treg depletion resulted in differentiation of inflammatory fibroblast subsets, in turn driving infiltration of myeloid cells through CCR1, thus uncovering a potentially new therapeutic approach to relieve immunosuppression in pancreatic cancer.

See related commentary by Aykut et al., p. 345.

This article is highlighted in the In This Issue feature, p. 327
Data from Gain-of-Function RHOA Mutations Promote Focal Adhesion Kinase Activation and Dependency in Diffuse Gastric Cancer
Authors: Zhang Haisheng , Schaefer Antje , Wang Yichen , Hodge Richard G. , Blake Devon R. , Diehl J. Nathaniel , Papageorge Alex G. , Stachler Matthew D. , Liao Jennifer , Zhou Jin , Wu Zhong , Akarca Fahire G. , de Klerk Leonie K. , Derks Sarah , Pierobon Mariaelena , Hoadley Katherine A. , Wang Timothy C. , Church George , Wong Kwok-Kin , Petricoin Emanuel F. , Cox Adrienne D. , Lowy Douglas R. , Der Channing J. , Bass Adam J.
Published: April 2023

Abstract
Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that of highly recurrent missense mutations in the GTPase RHOA. The function of these mutations has remained unresolved. We demonstrate that RHOAY42C, the most common RHOA mutation in DGC, is a gain-of-function oncogenic mutant, and that expression of RHOAY42C with inactivation of the canonical tumor suppressor Cdh1 induces metastatic DGC in a mouse model. Biochemically, RHOAY42C exhibits impaired GTP hydrolysis and enhances interaction with its effector ROCK. RHOAY42C mutation and Cdh1 loss induce actin/cytoskeletal rearrangements and activity of focal adhesion kinase (FAK), which activates YAP–TAZ, PI3K–AKT, and β-catenin. RHOAY42C murine models were sensitive to FAK inhibition and to combined YAP and PI3K pathway blockade. These results, coupled with sensitivity to FAK inhibition in patient-derived DGC cell lines, nominate FAK as a novel target for these cancers.
Significance:
The functional significance of recurrent RHOA mutations in DGC has remained unresolved. Through biochemical studies and mouse modeling of the hotspot RHOAY42C mutation, we establish that these mutations are activating, detail their effects upon cell signaling, and define how RHOA-mediated FAK activation imparts sensitivity to pharmacologic FAK inhibitors.

See related commentary by Benton and Chernoff, p. 182.

This article is highlighted in the In This Issue feature, p. 161
Data from TBK1 Is a Synthetic Lethal Target in Cancer with VHL Loss
Authors: Hu Lianxin , Xie Haibiao , Liu Xijuan , Potjewyd Frances , James Lindsey I. , Wilkerson Emily M. , Herring Laura E. , Xie Ling , Chen Xian , Cabrera Johnny Castillo , Hong Kai , Liao Chengheng , Tan Xianming , Baldwin Albert S. , Gong Kan , Zhang Qing
Published: April 2023

Abstract
TANK binding kinase 1 (TBK1) is an important kinase involved in the innate immune response. Here we discover that TBK1 is hyperactivated by von Hippel-Lindau (VHL) loss or hypoxia in cancer cells. Tumors from patients with kidney cancer with VHL loss display elevated TBK1 phosphorylation. Loss of TBK1 via genetic ablation, pharmacologic inhibition, or a new cereblon-based proteolysis targeting chimera specifically inhibits VHL-deficient kidney cancer cell growth, while leaving VHL wild-type cells intact. TBK1 depletion also significantly blunts kidney tumorigenesis in an orthotopic xenograft model in vivo. Mechanistically, TBK1 hydroxylation on Proline 48 triggers VHL as well as the phosphatase PPM1B binding that leads to decreased TBK1 phosphorylation. We identify that TBK1 phosphorylates p62/SQSTM1 on Ser366, which is essential for p62 stability and kidney cancer cell proliferation. Our results establish that TBK1, distinct from its role in innate immune signaling, is a synthetic lethal target in cancer with VHL loss.
Significance:
The mechanisms that lead to TBK1 activation in cancer and whether this activation is connected to its role in innate immunity remain unclear. Here, we discover that TBK1, distinct from its role in innate immunity, is activated by VHL loss or hypoxia in cancer.

See related commentary by Bakouny and Barbie, p. 348.

This article is highlighted in the In This Issue feature, p. 327