![]() ![]() Electronic address: onĬD8 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.ĬCR6 CD8 T cell TCF1 Tc17 checkpoint blockade immunodominance lung cancer neoantigen vaccine.Ĭopyright © 2021 Elsevier Inc. All rights reserved.ĭeclaration of interests T.J. Is on the board of directors of Amgen and ThermoFisher Scientific, a co-founder of Dragonfly Therapeutics and T2 Biosystems, an SAB member of Dragonfly Therapeutics, SQZ Biotech, and Skyhawk Therapeutics and is president of Break Through Cancer. ![]()
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