Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

Medientyp: E-Artikel

Titel: Tumor reactive γδ T cells contribute to a complete response to PD-1 blockade in a Merkel cell carcinoma patient

Beteiligte: Lien, Scott C.; Ly, Dalam; Yang, S. Y. Cindy; Wang, Ben X.; Clouthier, Derek L.; St. Paul, Michael; Gadalla, Ramy; Noamani, Babak; Garcia-Batres, Carlos R.; Boross-Harmer, Sarah; Bedard, Philippe L.; Pugh, Trevor J.; Spreafico, Anna; Hirano, Naoto; Razak, Albiruni R. A.; Ohashi, Pamela S.

Erschienen: Springer Science and Business Media LLC, 2024

Sprache: Englisch

DOI: 10.1038/s41467-024-45449-y

ISSN: 2041-1723

Schlagwörter: General Physics and Astronomy ; General Biochemistry, Genetics and Molecular Biology ; General Chemistry ; Multidisciplinary

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Beschreibung: AbstractImmunotherapies targeting PD-1/PD-L1 are now widely used in the clinic to treat a variety of malignancies. While most of the research on T cell exhaustion and PD-1 blockade has been focused on conventional αβ T cells, the contribution of innate-like T cells such as γδ T cells to anti-PD-1/PD-L1 mediated therapy is limited. Here we show that tumor reactive γδ T cells respond to PD-1 blockade in a Merkel cell carcinoma (MCC) patient experiencing a complete response to therapy. We find clonally expanded γδ T cells in the blood and tumor after pembrolizumab treatment, and this Vγ2Vδ1 clonotype recognizes Merkel cancer cells in a TCR-dependent manner. Notably, the intra-tumoral γδ T cells in the MCC patient are characterized by higher expression of PD-1 and TIGIT, relative to conventional CD4 and CD8 T cells. Our results demonstrate that innate-like T cells could also contribute to an anti-tumor response after PD-1 blockade.

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