Cutting Edge: Promoting T Cell Factor 1+ T Cell Self-Renewal to Improve Programmed Cell Death Protein 1 Blockade
| Autor: | Peter H. Wang, Robert Washburn, Rohan Maniar, Michael Mu, Olivia Ringham, Radomir Kratchmarov, Brian S. Henick, Steven L. Reiner |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 209:660-664 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Immune checkpoint blockade is limited by resistance to treatment, with many patients not achieving durable antitumor responses. Self-renewing (T cell factor 1+ [TCF1+]) CD8+ T cells have recently been implicated in efficacy of anti–programmed cell death protein 1 (anti–PD-1). Mice challenged with syngeneic tumors were treated with anti–PD-1 and/or a reversible inhibitor of PI3K δ, designed to promote T cell self-renewal. Growth of tumors in untreated mice was characterized by waning proportions of TCF1+ T cells, suggesting self-renewing T cells become limiting for successful immunotherapy. Higher proportions of TCF1+ T cells in tumor and blood correlated with better control of tumor growth. Combining anti–PD-1 and inhibitor of PI3K δ conferred superior protection compared with either monotherapy and was associated with higher frequency of TCF1+ T cells in tumor and blood compared with anti–PD-1 alone. These findings reveal predictive importance of self-renewing T cells in anti-tumor immunity and suggest that resistance-directed strategies to enhance T cell self-renewal could potentiate the efficacy of PD-1 blockade. |
| Databáze: | OpenAIRE |
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