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Table of Contents

In This Issue

  • In This Issue
    In This Issue
    Cancer Discov March 1 2021 11 (3) 521-523; DOI:10.1158/2159-8290.CD-ITI2021-0102

In the Spotlight

In Focus

  • In Focus
    Maturation Block in Childhood Cancer
    Sam Behjati, Richard J. Gilbertson and Stefan M. Pfister
    Cancer Discov March 1 2021 11 (3) 542-544; DOI:10.1158/2159-8290.CD-20-0926

Reviews

Research Briefs

  • Research Briefs | AuthorChoice
    Genetic Ancestry Contributes to Somatic Mutations in Lung Cancers from Admixed Latin American Populations
    Jian Carrot-Zhang, Giovanny Soca-Chafre, Nick Patterson, Aaron R. Thorner, Anwesha Nag, Jacqueline Watson, Giulio Genovese, July Rodriguez, Maya K. Gelbard, Luis Corrales-Rodriguez, Yoichiro Mitsuishi, Gavin Ha, Joshua D. Campbell, Geoffrey R. Oxnard, Oscar Arrieta, Andres F. Cardona, Alexander Gusev and Matthew Meyerson
    Cancer Discov March 1 2021 11 (3) 591-598; DOI:10.1158/2159-8290.CD-20-1165

    Tumor sequencing data from patients with lung cancer from Latin America revealed that Native American ancestry significantly affected tumors' somatic mutation profiles; the observed disparities arose from germline differences rather than environmental exposures.

  • Research Briefs
    A Critical Role for Fas-Mediated Off-Target Tumor Killing in T-cell Immunotherapy
    Ranjan Upadhyay, Jonathan A. Boiarsky, Gvantsa Pantsulaia, Judit Svensson-Arvelund, Matthew J. Lin, Aleksandra Wroblewska, Sherry Bhalla, Nathalie Scholler, Adrian Bot, John M. Rossi, Norah Sadek, Samir Parekh, Alessandro Lagana, Alessia Baccarini, Miriam Merad, Brian D. Brown and Joshua D. Brody
    Cancer Discov March 1 2021 11 (3) 599-613; DOI:10.1158/2159-8290.CD-20-0756

    Apoptotic FAS–FASL signaling enabled CD8+ T cells to exert cytotoxic effects on antigen-negative “bystander” tumor cells in vivo, possibly explaining how antigen-specific chimeric antigen receptor T-cell therapies can eliminate tumors with heterogeneous antigen expression.

  • Research Briefs | AuthorChoice
    A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor–Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention
    Spencer C. Wei, Wouter C. Meijers, Margaret L. Axelrod, Nana-Ama A.S. Anang, Elles M. Screever, Elizabeth C. Wescott, Douglas B. Johnson, Elizabeth Whitley, Lorenz Lehmann, Pierre-Yves Courand, James J. Mancuso, Lauren E. Himmel, Benedicte Lebrun-Vignes, Matthew J. Wleklinski, Bjorn C. Knollmann, Jayashree Srinivasan, Yu Li, Oluwatomisin T. Atolagbe, Xiayu Rao, Yang Zhao, Jing Wang, Lauren I.R. Ehrlich, Padmanee Sharma, Joe-Elie Salem, Justin M. Balko, Javid J. Moslehi and James P. Allison
    Cancer Discov March 1 2021 11 (3) 614-625; DOI:10.1158/2159-8290.CD-20-0856

    A new mouse model of immune checkpoint inhibitor–induced myocarditis was developed, enabling the discovery that abatacept may be useful for ameliorating this condition; this finding was supported by results from a patient case series.

Research Articles

  • Research Articles | AuthorChoice
    Poor Survival and Differential Impact of Genetic Features of Black Patients with Acute Myeloid Leukemia
    Bhavana Bhatnagar, Jessica Kohlschmidt, Krzysztof Mrózek, Qiuhong Zhao, James L. Fisher, Deedra Nicolet, Christopher J. Walker, Alice S. Mims, Christopher Oakes, Brian Giacopelli, Shelley Orwick, Isaiah Boateng, James S. Blachly, Sophia E. Maharry, Andrew J. Carroll, Bayard L. Powell, Jonathan E. Kolitz, Richard M. Stone, John C. Byrd, Electra D. Paskett, Albert de la Chapelle, Ramiro Garzon and Ann-Kathrin Eisfeld
    Cancer Discov March 1 2021 11 (3) 626-637; DOI:10.1158/2159-8290.CD-20-1579

    Black patients with AML fared worse than white patients, a trend that held true after adjusting for socioeconomic status and molecular features, and the impact of common prognosticating mutations (e.g., those in NPM1) differed between the two groups.

  • Research Articles | AuthorChoice
    Aggressive PDACs Show Hypomethylation of Repetitive Elements and the Execution of an Intrinsic IFN Program Linked to a Ductal Cell of Origin
    Elisa Espinet, Zuguang Gu, Charles D. Imbusch, Nathalia A. Giese, Magdalena Büscher, Mariam Safavi, Silke Weisenburger, Corinna Klein, Vanessa Vogel, Mattia Falcone, Jacob Insua-Rodríguez, Manuel Reitberger, Vera Thiel, Steffi O. Kossi, Alexander Muckenhuber, Karnjit Sarai, Alex Y.L. Lee, Elyne Backx, Soheila Zarei, Matthias M. Gaida, Manuel Rodríguez-Paredes, Elisa Donato, Hsi-Yu Yen, Roland Eils, Matthias Schlesner, Nicole Pfarr, Thilo Hackert, Christoph Plass, Benedikt Brors, Katja Steiger, Dieter Weichenhan, H. Efsun Arda, Ilse Rooman, Janel L. Kopp, Oliver Strobel, Wilko Weichert, Martin R. Sprick and Andreas Trumpp
    Cancer Discov March 1 2021 11 (3) 638-659; DOI:10.1158/2159-8290.CD-20-1202

    Transcriptomic and DNA methylomic analyses revealed the existence of an aggressive, ductal cell–derived pancreatic ductal adenocarcinoma subgroup defined by low methylation of repetitive elements and expression of an IFN-linked transcriptional program.

  • Research Articles
    Cell of Origin Influences Pancreatic Cancer Subtype
    Brittany M. Flowers, Hang Xu, Abigail S. Mulligan, Kathryn J. Hanson, Jose A. Seoane, Hannes Vogel, Christina Curtis, Laura D. Wood and Laura D. Attardi
    Cancer Discov March 1 2021 11 (3) 660-677; DOI:10.1158/2159-8290.CD-20-0633

    Pancreatic ductal adenocarcinomas in adult genetically engineered mice could arise from either ductal or acinar cells, and tumors arising from each cell type had distinct transcriptional profiles that matched those of defined human pancreatic cancer subtypes.

  • Research Articles | AuthorChoice
    The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis
    Xin Hong, Whijae Roh, Ryan J. Sullivan, Keith H.K. Wong, Ben S. Wittner, Hongshan Guo, Taronish D. Dubash, Moshe Sade-Feldman, Benjamin Wesley, Elad Horwitz, Genevieve M. Boland, Dieuwke L. Marvin, Todd Bonesteel, Chenyue Lu, François Aguet, Risa Burr, Samuel S. Freeman, Laxmi Parida, Katherine Calhoun, Michelle K. Jewett, Linda T. Nieman, Nir Hacohen, Anders M. Näär, David T. Ting, Mehmet Toner, Shannon L. Stott, Gad Getz, Shyamala Maheswaran and Daniel A. Haber
    Cancer Discov March 1 2021 11 (3) 678-695; DOI:10.1158/2159-8290.CD-19-1500

    Melanoma circulating tumor cells (CTC) prevented ferroptotic death by upregulating SREBF2-mediated lipogenic pathways and iron homeostatic pathways, and blocking this escape mechanism by knocking out the gene encoding transferrin hindered CTC tumor formation.

  • Research Articles | AuthorChoice
    An Empirical Antigen Selection Method Identifies Neoantigens That Either Elicit Broad Antitumor T-cell Responses or Drive Tumor Growth
    Hubert Lam, Lisa K. McNeil, Hanna Starobinets, Victoria L. DeVault, Roger B. Cohen, Przemyslaw Twardowski, Melissa L. Johnson, Maura L. Gillison, Mark N. Stein, Ulka N. Vaishampayan, Arthur P. DeCillis, James J. Foti, Vijetha Vemulapalli, Emily Tjon, Kyle Ferber, Daniel B. DeOliveira, Wendy Broom, Parul Agnihotri, Elizabeth M. Jaffee, Kwok-Kin Wong, Charles G. Drake, Pamela M. Carroll, Thomas A. Davis and Jessica Baker Flechtner
    Cancer Discov March 1 2021 11 (3) 696-713; DOI:10.1158/2159-8290.CD-20-0377

    An ex vivo bioassay, ATLAS, was able to identify stimulatory and inhibitory neoantigens for the design of personalized anticancer vaccines; this assay pinpointed anti- and protumorigenic antigens, as demonstrated via in vivo experiments.

  • Research Articles | AuthorChoice
    Durable Suppression of Acquired MEK Inhibitor Resistance in Cancer by Sequestering MEK from ERK and Promoting Antitumor T-cell Immunity
    Aayoung Hong, Marco Piva, Sixue Liu, Willy Hugo, Shirley H. Lomeli, Vincent Zoete, Christopher E. Randolph, Zhentao Yang, Yan Wang, Jordan J. Lee, Skylar J. Lo, Lu Sun, Agustin Vega-Crespo, Alejandro J. Garcia, David B. Shackelford, Steven M. Dubinett, Philip O. Scumpia, Stephanie D. Byrum, Alan J. Tackett, Timothy R. Donahue, Olivier Michielin, Sheri L. Holmen, Antoni Ribas, Gatien Moriceau and Roger S. Lo
    Cancer Discov March 1 2021 11 (3) 714-735; DOI:10.1158/2159-8290.CD-20-0873

    Type II RAF inhibitors provided distinct advantages over Type I RAF inhibitors when used in combination with MEK inhibitors in models with MAPK pathway alterations.

  • Research Articles | AuthorChoice
    Epigenetic and Transcriptional Control of the Epidermal Growth Factor Receptor Regulates the Tumor Immune Microenvironment in Pancreatic Cancer
    Jinyang Li, Salina Yuan, Robert J. Norgard, Fangxue Yan, Yu H. Sun, Il-Kyu Kim, Allyson J. Merrell, Yogev Sela, Yanqing Jiang, Natarajan V. Bhanu, Benjamin A. Garcia, Robert H. Vonderheide, Andrés Blanco and Ben Z. Stanger
    Cancer Discov March 1 2021 11 (3) 736-753; DOI:10.1158/2159-8290.CD-20-0519

    A screen for tumor cell–intrinsic suppressors of antitumor immunity identified the histone methyltransferase KDM3A, which activated the expression of EGFR to keep the tumor immune microenvironment in a non–T-cell-inflamed state.

  • Research Articles | AuthorChoice
    Phenotypic Mapping of Pathologic Cross-Talk between Glioblastoma and Innate Immune Cells by Synthetic Genetic Tracing
    Matthias Jürgen Schmitt, Carlos Company, Yuliia Dramaretska, Iros Barozzi, Andreas Göhrig, Sonia Kertalli, Melanie Großmann, Heike Naumann, Maria Pilar Sanchez-Bailon, Danielle Hulsman, Rainer Glass, Massimo Squatrito, Michela Serresi and Gaetano Gargiulo
    Cancer Discov March 1 2021 11 (3) 754-777; DOI:10.1158/2159-8290.CD-20-0219

    A genetic tracing method using synthetic reporters comprised of glioblastoma subtypespecific cis-regulatory elements allowed mapping of cell states and fate transitions.

  • Research Articles | AuthorChoice
    Machine-Learning and Chemicogenomics Approach Defines and Predicts Cross-Talk of Hippo and MAPK Pathways
    Trang H. Pham, Thijs J. Hagenbeek, Ho-June Lee, Jason Li, Christopher M. Rose, Eva Lin, Mamie Yu, Scott E. Martin, Robert Piskol, Jennifer A. Lacap, Deepak Sampath, Victoria C. Pham, Zora Modrusan, Jennie R. Lill, Christiaan Klijn, Shiva Malek, Matthew T. Chang and Anwesha Dey
    Cancer Discov March 1 2021 11 (3) 778-793; DOI:10.1158/2159-8290.CD-20-0706

    A lineage-independent, unbiased approach to characterize Hippo pathway activity and dependency identified cross-talk between the Hippo and MAPK pathways and suggested a potential therapeutic strategy for Hippodependent cancers.

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