PerspectiveImmunology

Killer cells add fire to fuel immunotherapy

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Science  29 May 2020:
Vol. 368, Issue 6494, pp. 943-944
DOI: 10.1126/science.abc2502

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Summary

Cytotoxic lymphocytes, including natural killer (NK) cells and cytotoxic T lymphocytes (CTLs or CD8+ T cells), mediate antiviral and antitumoral immunity. Target cell killing by CTLs and NK cells is primarily mediated through the release of cytotoxic granules that contain serine proteases called granzymes and a pore-forming protein, perforin. Perforin delivers granzyme B (GZMB) into target cells, where it initiates apoptosis, a noninflammatory form of programmed cell death (1, 2). On page 965 of this issue, Zhou et al. (3) report their discovery of a new mechanism of cytotoxicity in which granzyme A (GZMA), delivered to certain target cells by NK cells and CTLs, activates gasdermin B (GSDMB), a pore-forming protein, which causes a proinflammatory form of cell death called pyroptosis (4). Expression of GSDMB by mouse tumor cells conferred better tumor control in response to immune checkpoint therapy.

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