AUTHOR=Manoharan Malini , Mandloi Nitin , Priyadarshini Sushri , Patil Ashwini , Gupta Rohit , Iyer Laxman , Gupta Ravi , Chaudhuri Amitabha 

TITLE=A Computational Approach Identifies Immunogenic Features of Prognosis in Human Cancers

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.03017

DOI=10.3389/fimmu.2018.03017

ISSN=1664-3224

ABSTRACT=<p>A large number of tumor intrinsic and extrinsic factors determine long-term survival in human cancers. In this study, we stratified 9120 tumors from 33 cancers with respect to their immune cell content and identified immunogenomic features associated with long-term survival. Our analysis demonstrates that tumors infiltrated by CD8<sup>+</sup> T cells expressing higher levels of activation marker (PD1<sup>hi</sup>) along with TCR signaling genes and cytolytic T cell markers (IL2<sup>hi</sup>/TNF-α<sup>hi</sup>/IFN-γ<sup>hi</sup>/GZMA-B<sup>hi</sup>) extend survival, whereas survival benefit was absent for tumors infiltrated by anergic and hyperexhausted CD8<sup>+</sup> T cells characterized by high expression of <italic>CTLA-4, TIM3, LAG3</italic>, and genes linked to PI3K signaling pathway. The computational approach of using robust and highly specific gene expression signatures to deconvolute the tumor microenvironment has important clinical applications, such as selecting patients who will benefit from checkpoint inhibitor treatment.</p>