Pan-cancer immune and stromal deconvolution predicts clinical outcomes and mutation profiles
Bhavneet Bhinder(Cornell University), Verena Friedl(University of California, Santa Cruz), Sunantha Sethuraman(Washington University in St. Louis), Davide Risso(University of Padua), Kami Chiotti(Oregon Health & Science University), R. Jay Mashl(James S. McDonnell Foundation), Kyle Ellrott(Oregon Health & Science University), Jordan Lee(Oregon Health & Science University), Christopher K. Wong(University of California, Santa Cruz), Kofi K. Gyan(Cornell University), Aditya Deshpande(Cornell University), Marcin Imieliński(Cornell University), Rohan Bareja(Cornell University), Joshua M. Stuart(University of California, Santa Cruz), Myron Peto(Oregon Health & Science University), Katherine A. Hoadley(University of North Carolina at Chapel Hill), Alexander J. Lazar(The University of Texas MD Anderson Cancer Center), Andrew D. Cherniack(Broad Institute), Jingchun Zhu(University of California, Santa Cruz), Shaolong Cao(The University of Texas MD Anderson Cancer Center), Mark Rubin(University of Bern), Wenyi Wang(The University of Texas MD Anderson Cancer Center), Oliver F. Bathe(University of Calgary), Nicolas Robine(New York Genome Center), Li Ding(James S. McDonnell Foundation), Peter W. Laird(Van Andel Institute), Wanding Zhou(Van Andel Institute), Hui Shen(Van Andel Institute), Vésteinn Thórsson(Institute for Systems Biology), Jen Jen Yeh(University of North Carolina at Chapel Hill), Matthew H. Bailey(James S. McDonnell Foundation), Daniel Cui Zhou(James S. McDonnell Foundation), Xianlu L. Peng(University of North Carolina at Chapel Hill), Mary J. Goldman(University of California, Santa Cruz), Yongsheng Li(The University of Texas MD Anderson Cancer Center), Anil Korkut(The University of Texas MD Anderson Cancer Center), Nidhi Sahni(The University of Texas MD Anderson Cancer Center), D. Neil Hayes(University of Tennessee Health Science Center), Michael K. A. Mensah(National Cancer Institute), Ina Felau(National Cancer Institute), Anab Kemal(National Cancer Institute), Rory Johnson(National Cancer Institute), John A. Demchok(National Cancer Institute), Liming Yang(National Cancer Institute), Martin L. Ferguson(National Cancer Institute), Roy Tarnuzzer(National Cancer Institute), Zhining Wang(National Cancer Institute), Jean C. Zenklusen(National Cancer Institute), The Cancer Genome Atlas Analysis Network(Oregon Health & Science University), Adam Margolin(Oregon Health & Science University), Alana Weinstein(University of California, Santa Cruz), Andrea Sboner(Cornell University), Andrew Blair(University of California, Santa Cruz), Angela Brooks(University of California, Santa Cruz), Benjamin Berman(Van Andel Institute), Benjamin Raphael(Princeton University), Brian Craft(University of California, Santa Cruz), Dante Bortone(University of North Carolina at Chapel Hill), David Heimain(Broad Institute), David Gibbs(Institute for Systems Biology), David Haan(University of California, Santa Cruz), Doron Betel(Cornell University), Duncan McColl(University of California, Santa Cruz), Emek Demir(Oregon Health & Science University), Faeze Brahman(University of California, Santa Cruz), Farshad Farshidfar(University of Calgary), Gaddy Getz(Broad Institute), Galen Gao(Broad Institute), Gordon Robertson(Institute for Systems Biology), Huy Dinh(Van Andel Institute), Hyo Young Choi(University of North Carolina at Chapel Hill), Ilya Shmulevich(Institute for Systems Biology), Ioannis Anastopoulous(University of California, Santa Cruz), Jasmine Yang(The University of Texas MD Anderson Cancer Center), Jeff Damrauer(University of North Carolina at Chapel Hill), Ken Chen(The University of Texas MD Anderson Cancer Center), Lauren Sanders(University of California, Santa Cruz), Lee Cooper(Emory University), Liang-Bo Wang(Washington University in St. Louis), Matt Reyna(Princeton University), Mike Noble(Broad Institute), Mohammed El-Kebir(Princeton University), Molly Zhang(University of California, Santa Cruz), Nicole Yeager(Van Andel Institute), Paul Little(University of North Carolina at Chapel Hill), Richard Moffitt(Princeton University), Sam Meier(Broad Institute), Teresa Swatloski(University of California, Santa Cruz), Theo Knijnenburg(Institute for Systems Biology), Thomas Matthew(University of California, Santa Cruz), Vicky Chen(University of Pittsburgh), Vlado Uzunangelov(University of California, Santa Cruz), Xinghua Lu(University of Pittsburgh), Yige Wu(Washington University in St. Louis), Yulia Newton(University of California, Santa Cruz), Zeya Wang(National Cancer Institute), Paul Spellman(Oregon Health & Science University), Olivier Elemento(Cornell University)
Cited by 4Open Access
Abstract
Traditional gene expression deconvolution methods assess a limited number of cell types, therefore do not capture the full complexity of the tumor microenvironment (TME). Here, we integrate nine deconvolution tools to assess 79 TME cell types in 10,592 tumors across 33 different cancer types, creating the most comprehensive analysis of the TME. In total, we found 41 patterns of immune infiltration and stroma profiles, identifying heterogeneous yet unique TME portraits for each cancer and several new findings. Our findings indicate that leukocytes play a major role in distinguishing various tumor types, and that a shared immune-rich TME cluster predicts better survival in bladder cancer for luminal and basal squamous subtypes, as well as in melanoma for RAS-hotspot subtypes. Our detailed deconvolution and mutational correlation analyses uncover 35 therapeutic target and candidate response biomarkers hypotheses (including CASP8 and RAS pathway genes).