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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.03017

A computational approach identifies immunogenic features of prognosis in human cancers

 Malini Manhoharan1,  Nitin Mandloi1, Sushri Priyadarshini1,  Rohit Gupta1, Laxman Iyer1,  Ravi Gupta1* and  Amitabha Chaudhuri2*
  • 1Medgenome Pvt. Ltd, India
  • 2MedGenome Inc., United States

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+ T cells expressing higher levels of activation marker (PD1hi) along with TCR signaling genes and cytolytic T cell markers (IL2hi/TNF-αhi/IFN-γhi/GZMA-Bhi) extend survival, whereas survival benefit was absent for tumors infiltrated by anergic and hyperexhausted CD8+ T cells characterized by high expression of CTLA-4, TIM3, LAG3 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.

Keywords: Tumor Microenvironment, Gene signatures, Inflamed tumors, Immune infiltration, prognosis

Received: 12 Aug 2018; Accepted: 06 Dec 2018.

Edited by:

Andreas Pircher, Innsbruck Medical University, Austria

Reviewed by:

Hermann Frieboes, University of Louisville, United States
Bernard Thienpont, Faculty of Medicine, KU Leuven, Belgium  

Copyright: © 2018 Manhoharan, Mandloi, Priyadarshini, Gupta, Iyer, Gupta and Chaudhuri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Ravi Gupta, Medgenome Pvt. Ltd, Bengaluru, 560099, Karnataka, India, ravig@medgenome.com
Dr. Amitabha Chaudhuri, MedGenome Inc., Foster City, United States, amitc@medgenome.com