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Merck

Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors.

Cell (2021-09-18)
Megan L Burger, Amanda M Cruz, Grace E Crossland, Giorgio Gaglia, Cecily C Ritch, Sarah E Blatt, Arjun Bhutkar, David Canner, Tamina Kienka, Sara Z Tavana, Alexia L Barandiaran, Andrea Garmilla, Jason M Schenkel, Michelle Hillman, Izumi de Los Rios Kobara, Amy Li, Alex M Jaeger, William L Hwang, Peter M K Westcott, Michael P Manos, Marta M Holovatska, F Stephen Hodi, Aviv Regev, Sandro Santagata, Tyler Jacks
RESUMO

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.

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Roche
DNase I, grade II, from bovine pancreas
SKU
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