Pan-cancer immune and stromal deconvolution predicts clinical outcomes and mutation profiles
Abstract
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).
Article Details
Authors (97)
Bhavneet Bhinder
Verena Friedl
Sunantha Sethuraman
Davide Risso
Kami E. Chiotti
R. Jay Mashl
Kyle P. Ellrott
Jordan A. Lee
Christopher K. Wong
Kofi Gyan
Aditya Deshpande
Marcin Imielinski
Rohan Bareja
Josh Stuart
Myron Peto
Katherine A. Hoadley
Alexander J. Lazar
Andrew D. Cherniack
Jingchun Zhu
Shaolong Cao
Mark Rubin
Wenyi Wang
Oliver F. Bathe
Nicolas Robine
Li Ding
Peter W. Laird
Wanding Zhou
Hui Shen
Vésteinn Thorsson
Jen Jen Yeh
Matthew H. Bailey
Daniel Cui Zhou
Xianlu L. Peng
Mary Goldman
Yongsheng Li
Department of Chemistry, State Key Lab of Molecular Engineering of Polymers, and Shanghai Key Lab of Molecular Catalysis and Innovative Materials
Anil Korkut
Nidhi Sahni
D. Neil Hayes
Michael K. A. Mensah
Ina Felau
Anab Kemal
Samantha Caesar-Johnson
John A. Demchok
Liming Yang
Martin L. Ferguson
Roy Tarnuzzer
Zhining Wang
Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering
Jean C. Zenklusen
Adam Margolin
Alana Weinstein
Andrea Sboner
Andrew Blair
Angela Brooks
Benjamin Berman
Benjamin Raphael
Brian Craft
Dante Bortone
David Heimain
David Gibbs
David Haan
Doron Betel
Duncan McColl
Emek Demir
Faeze Brahman
Farshad Farshidfar
Gaddy Getz
Galen Gao
Gordon Robertson
Huy Dinh
Hyo Young Choi
Ilya Shmulevich
Ioannis Anastopoulous
Jasmine Yang
Jeff Damrauer
Ken Chen
Lauren Sanders
Lee Cooper
Liang-Bo Wang
Matt Reyna
Mike Noble
Mohammed El-Kebir
Molly Zhang
Nicole Yeager
Paul Little
Richard Moffitt
Sam Meier
Teresa Swatloski
Theo Knijnenburg
Thomas Matthew
Vicky Chen
Vlado Uzunangelov
Xinghua Lu
Yige Wu
Yulia Newton
Zeya Wang
Paul Spellman
Olivier Elemento