Journal
BIOESSAYS
Volume 42, Issue 10, Pages -Publisher
WILEY
DOI: 10.1002/bies.202000024
Keywords
cancer immunology; heterogeneity of anti-tumor immunity; TCR repertoire; tumor immunogenicity
Categories
Funding
- University of Colorado School of Medicine and Cancer Center startup funds
- THI pilot grant
- NIH [R01-DE027329, R01-DE028420, R21-CA184707, R21-AI110777, R01-CA166325, R01-CA229174, R01-CA249940]
- Cancer League of Colorado
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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.
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