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1 August 2019
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Elyada and colleagues profiled human pancreatic ductal adenocarcinoma tumors and adjacent normal tissue along with mouse pancreatic tumors and discovered a previously unknown class of cancer-associated fibroblasts (CAF) they named antigen-presenting CAFs (apCAF). These CAFs are unique in their expression of MHC class II–related genes, which implies they may interact with CD4+ T cells; supporting this idea, apCAFs activated CD4+ T cells ex vivo in an antigen-dependent fashion. Also unlike other CAFs, apCAFs upregulate MYC targets and antigen presentation, antigen processing, fatty-acid metabolism, and MTORC1 signaling pathways. Hinting that apCAFs may contribute to immune suppression in PDAC, they do not produce costimulatory molecules needed for induction of T-cell proliferation For details, please see the article by Elyada and colleagues on page 1102. - PDF Icon PDF LinkTable of Contents
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ISSN 2159-8274
EISSN 2159-8290
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Research Brief
Unique Neoantigens Arise from Somatic Mutations in Patients with Gastrointestinal Cancers
Maria R. Parkhurst; Paul F. Robbins; Eric Tran; Todd D. Prickett; Jared J. Gartner; Li Jia; Gabriel Ivey; Yong F. Li; Mona El-Gamil; Almin Lalani; Jessica S. Crystal; Abraham Sachs; Eric Groh; Satyajit Ray; Lien T. Ngo; Scott Kivitz; Anna Pasetto; Rami Yossef; Frank J. Lowery; Stephanie L. Goff; Winifred Lo; Gal Cafri; Drew C. Deniger; Parisa Malekzadeh; Mojgan Ahmadzadeh; John R. Wunderlich; Robert P.T. Somerville; Steven A. Rosenberg
Research Articles
Author Choice
First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematologic Cancers: Results of a Phase I Dose-Escalation Study
Amit Khot; Natalie Brajanovski; Donald P. Cameron; Nadine Hein; Kylee H. Maclachlan; Elaine Sanij; John Lim; John Soong; Emma Link; Piers Blombery; Ella R. Thompson; Andrew Fellowes; Karen E. Sheppard; Grant A. McArthur; Richard B. Pearson; Ross D. Hannan; Gretchen Poortinga; Simon J. Harrison
Clonal Selection with RAS Pathway Activation Mediates Secondary Clinical Resistance to Selective FLT3 Inhibition in Acute Myeloid Leukemia
Christine M. McMahon; Timothy Ferng; Jonathan Canaani; Eunice S. Wang; Jennifer J.D. Morrissette; Dennis J. Eastburn; Maurizio Pellegrino; Robert Durruthy-Durruthy; Christopher D. Watt; Saurabh Asthana; Elisabeth A. Lasater; RosaAnna DeFilippis; Cheryl A.C. Peretz; Lisa H.F. McGary; Safoora Deihimi; Aaron C. Logan; Selina M. Luger; Neil P. Shah; Martin Carroll; Catherine C. Smith; Alexander E. Perl
Author Choice
TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion–Positive Intrahepatic Cholangiocarcinoma
Lipika Goyal; Lei Shi; Leah Y. Liu; Ferran Fece de la Cruz; Jochen K. Lennerz; Srivatsan Raghavan; Ignaty Leschiner; Liudmila Elagina; Giulia Siravegna; Raymond W.S. Ng; Phuong Vu; Krushna C. Patra; Supriya K. Saha; Raul N. Uppot; Ron Arellano; Stephanie Reyes; Takeshi Sagara; Sachie Otsuki; Brandon Nadres; Heather A. Shahzade; Ipsita Dey-Guha; Isobel J. Fetter; Islam Baiev; Emily E. Van Seventer; Janet E. Murphy; Cristina R. Ferrone; Kenneth K. Tanabe; Vikram Deshpande; James J. Harding; Rona Yaeger; Robin K. Kelley; Alberto Bardelli; A. John Iafrate; William C. Hahn; Cyril H. Benes; David T. Ting; Hiroshi Hirai; Gad Getz; Dejan Juric; Andrew X. Zhu; Ryan B. Corcoran; Nabeel Bardeesy
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia
Emmalee R. Adelman; Hsuan-Ting Huang; Alejandro Roisman; André Olsson; Antonio Colaprico; Tingting Qin; R. Coleman Lindsley; Rafael Bejar; Nathan Salomonis; H. Leighton Grimes; Maria E. Figueroa
Author Choice
Cross-Species Single-Cell Analysis of Pancreatic Ductal Adenocarcinoma Reveals Antigen-Presenting Cancer-Associated Fibroblasts
Ela Elyada; Mohan Bolisetty; Pasquale Laise; William F. Flynn; Elise T. Courtois; Richard A. Burkhart; Jonathan A. Teinor; Pascal Belleau; Giulia Biffi; Matthew S. Lucito; Santhosh Sivajothi; Todd D. Armstrong; Dannielle D. Engle; Kenneth H. Yu; Yuan Hao; Christopher L. Wolfgang; Youngkyu Park; Jonathan Preall; Elizabeth M. Jaffee; Andrea Califano; Paul Robson; David A. Tuveson
β-Catenin Activation Promotes Immune Escape and Resistance to Anti–PD-1 Therapy in Hepatocellular Carcinoma
Marina Ruiz de Galarreta; Erin Bresnahan; Pedro Molina-Sánchez; Katherine E. Lindblad; Barbara Maier; Daniela Sia; Marc Puigvehi; Verónica Miguela; María Casanova-Acebes; Maxime Dhainaut; Carlos Villacorta-Martin; Aatur D. Singhi; Akshata Moghe; Johann von Felden; Lauren Tal Grinspan; Shuang Wang; Alice O. Kamphorst; Satdarshan P. Monga; Brian D. Brown; Augusto Villanueva; Josep M. Llovet; Miriam Merad; Amaia Lujambio
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