TIGIT is a key inhibitory checkpoint receptor in lymphoma
| Autor: | Yuanyuan Zha, Xiufen Chen, James Godfrey, Girish Venkataraman, Justin P Kline, Aleksander Bagaev, Jovian Yu, Nicole Sunseri, Alan Cooper, Arina Varlamova, Dmitry Zarubin, Yuriy Popov, Connor Jacobson, Ekaterina Postovalova, Zhongmin Xiang, Krystle Nomie, Sravya Tumuluru, Sonali M Smith |
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| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 11, Iss 6 (2023) |
| Druh dokumentu: | article |
| ISSN: | 2022-0065 2051-1426 |
| DOI: | 10.1136/jitc-2022-006582 |
| Popis: | Background PD-1 checkpoint blockade therapy (CBT) has greatly benefited patients with select solid tumors and lymphomas but has limited efficacy against diffuse large B-cell lymphoma (DLBCL). Because numerous inhibitory checkpoint receptors have been implicated in driving tumor-specific T cell dysfunction, we hypothesized that combinatorial CBT would enhance the activity of anti-PD-1-based therapy in DLBCL. T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a coinhibitory receptor expressed on dysfunctional tumor-infiltrating T cells, and TIGIT blockade has demonstrated encouraging activity in combination with PD-1 blockade in murine tumor models and in clinical studies. However, the degree to which TIGIT mediates T cell dysfunction in DLBCL has not been fully explored.Results Here, we demonstrate that TIGIT is broadly expressed on lymphoma-infiltrating T cells (LITs) across a variety of human lymphomas and is frequently coexpressed with PD-1. TIGIT expression is particularly common on LITs in DLBCL, where TIGIT+ LITs often form distinct cellular communities and exhibit significant contact with malignant B cells. TIGIT+/PD-1+ LITs from human DLBCL and murine lymphomas exhibit hypofunctional cytokine production on ex vivo restimulation. In mice with established, syngeneic A20 B-cell lymphomas, TIGIT or PD-1 mono-blockade leads to modest delays in tumor outgrowth, whereas PD-1 and TIGIT co-blockade results in complete rejection of A20 lymphomas in most mice and significantly prolongs survival compared with mice treated with monoblockade therapy.Conclusions These results provide rationale for clinical investigation of TIGIT and PD-1 blockade in lymphomas, including DLBCL. |
| Databáze: | Directory of Open Access Journals |
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