Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions.

Transcription factors ThPOK and Runx3 regulate the differentiation of "helper" CD4+ and "cytotoxic" CD8+ T cell lineages respectively, inducing single positive (SP) T cells that enter the periphery with the expression of either the CD4 or CD8 co-receptor. Despite the expectation that these cell fates are mutually exclusive and that mature CD4+CD8+ double positive (DP) T cells are present in healthy individuals and augmented in the context of disease, yet their molecular features and pathophysiologic role are disputed. Here, we show DP T cells in murine and human tumors as a heterogenous population originating from SP T cells which re-express the opposite co-receptor and acquire features of the opposite cell type's phenotype and function following TCR stimulation. We identified distinct clonally expanded DP T cells in human melanoma and lung cancer by scRNA sequencing and demonstrated their tumor reactivity in cytotoxicity assays. Our findings indicate that antigen stimulation induces SP T cells to differentiate into DP T cell subsets gaining in polyfunctional characteristics. © 2022 Schad et al.

Citation

Sara E Schad, Andrew Chow, Levi Mangarin, Heng Pan, Jiajia Zhang, Nicholas Ceglia, Justina X Caushi, Nicole Malandro, Roberta Zappasodi, Mathieu Gigoux, Daniel Hirschhorn, Sadna Budhu, Masataka Amisaki, Monica Arniella, David Redmond, Jamie Chaft, Patrick M Forde, Justin F Gainor, Matthew D Hellmann, Vinod Balachandran, Sohrab Shah, Kellie N Smith, Drew Pardoll, Olivier Elemento, Jedd D Wolchok, Taha Merghoub. Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions. The Journal of experimental medicine. 2022 Jun 06;219(6)

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PMID: 35604411

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