Why the Outcome of Anti‐Tumor Immune Responses is Heterogeneous: A Novel Idea in the Context of Immunological Heterogeneity in Cancers. (7th August 2020)

• Record Type: Journal Article
• Authors: Wang, Jing H.
• Is Part Of: BioEssays. Volume 42:Number 10(2020:Oct.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-08-07
• Subjects: cancer immunology -- heterogeneity of anti‐tumor immunity -- TCR repertoire -- tumor immunogenicity; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202000024
• Languages: English
• ISSNs: 0265-9247

Abstract

Abstract: The question as to why some hosts can eradicate their tumors while others succumb to tumor‐progression remains unanswered. Here, a provocative concept is proposed that intrinsic differences in the T cell receptor (TCR) repertoire of individuals may influence the outcome of anti‐tumor immunity by affecting the frequency and/or variety of tumor‐reactive CD8 and/or CD4 tumor‐infiltrating lymphocytes. This idea implicates that the TCR repertoire in a given patient might not provide sufficiently different TCR clones that can recognize tumor antigens, namely, "a hole in the TCR repertoire" might exist. This idea may provide a novel perspective to further dissect the mechanisms underlying heterogeneous anti‐tumor immune responses in different hosts. Besides tumor‐intrinsic heterogeneity and host microbiome, the various factors that may constantly shape the dynamic TCR repertoire are also discussed. Elucidating mechanistic differences in different individuals' immune systems will allow to better harness immune system to design new personalized cancer immunotherapy. Abstract : Underlying mechanisms that dictate the immunological heterogeneity in cancers remain elusive. Besides tumor‐intrinsic heterogeneity and environmental factors, intrinsic differences in the T cell receptor (TCR) repertoire may play a role. "A hole in the TCR repertoire" hypothesis is proposed to explain heterogeneity of anti‐tumor responses that may significantly impact cancer immunotherapy.