Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions Journal Article
| Authors: | Schad, S. E.; Chow, A.; Mangarin, L.; Pan, H.; Zhang, J.; Ceglia, N.; Caushi, J. X.; Malandro, N.; Zappasodi, R.; Gigoux, M.; Hirschhorn, D.; Budhu, S.; Amisaki, M.; Arniella, M.; Redmond, D.; Chaft, J.; Forde, P. M.; Gainor, J. F.; Hellmann, M. D.; Balachandran, V.; Shah, S.; Smith, K. N.; Pardoll, D.; Elemento, O.; Wolchok, J. D.; Merghoub, T. |
| Article Title: | Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions |
| Abstract: | 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. |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 219 |
| Issue: | 6 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2022-06-06 |
| Language: | English |
| DOI: | 10.1084/jem.20212169 |
| PUBMED: | 35604411 |
| PROVIDER: | scopus |
| PMCID: | PMC9130031 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2022 -- Source: Scopus |
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