4.7 Article

Murine regulatory T cells utilize granzyme B to promote tumor metastasis

期刊

CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 72, 期 9, 页码 2927-2937

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SPRINGER
DOI: 10.1007/s00262-023-03410-w

关键词

Regulatory T cells (Tregs); Granzyme B (GzmB); Immune suppression; Tumor metastasis

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Regulatory T cells (Tregs) express Granzyme B (GzmB) and perforin, which were shown to inhibit tumor clearance. This study investigates the role of Treg-derived GzmB in tumor progression and metastasis, showing that it is important for spontaneous lung metastasis and increasing the metastatic burden.
Regulatory T cells (Tregs) possess a wide range of mechanisms for immune suppression. Among them, Granzyme B (GzmB) and perforin expressed by Tregs were shown to inhibit tumor clearance in previous reports, which contradicted the canonical roles of these cytotoxic molecules expressed by cytotoxic T cells and NK cells in antitumor immune responses. Given the ability of the tumor to manipulate the microenvironment, Treg-derived GzmB function may represent an important approach to aid in tumor growth as well as facilitating tumor metastasis. In this study, we utilized Treg-specific GzmB knockout (Foxp3(cre)GzmB(fl/fl)) mice to test whether Treg-derived GzmB can aid in tumor progression and metastasis. Using an IL-2 complex to activate GzmB expression in the non-immunogenic B16-F10 tumor model, we provide evidence to show that GzmB produced by Tregs is important for spontaneous metastasis to the lungs. In addition, we depleted CD8 + T cells to selectively measure the impact of Treg-derived GzmB in an experimental lung metastasis model by intravenous injection of B16-F10 tumor cells; our results demonstrate that Treg-derived GzmB plays an important role in increasing the metastatic burden to the lungs.

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