Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors
Name
nihms-1739841.pdf
Description
Accepted version
Size
3.54 MB
Format
Adobe PDF
Checksum (MD5)
dbec16c52784ba877bce1ba9f757ea91
Author(s)
Burger, Megan L
Cruz, Amanda M
Crossland, Grace E
Gaglia, Giorgio
Ritch, Cecily C
Blatt, Sarah E
Bhutkar, Arjun
Canner, David
Kienka, Tamina
Tavana, Sara Z
Date Issued
2021
Journal
Cell
Publisher
Elsevier BV
Citation
Burger, Megan L, Cruz, Amanda M, Crossland, Grace E, Gaglia, Giorgio, Ritch, Cecily C et al. 2021. "Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors." Cell, 184 (19).
Version
Author's final manuscript
Abstract
CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. T cells responding to subdominant antigens were enriched for a TCF1+ progenitor phenotype correlated with response to immune checkpoint blockade (ICB) therapy. However, the subdominant T cell response did not preferentially benefit from ICB due to a dysfunctional subset of TCF1+ cells marked by CCR6 and Tc17 differentiation. Analysis of human samples and sequencing datasets revealed that CCR6+ TCF1+ cells exist across human cancers and are not correlated with ICB response. Vaccination eliminated CCR6+ TCF1+ cells and dramatically improved the subdominant response, highlighting a strategy to optimally engage concurrent neoantigen responses against tumors.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELL.2021.08.020
