التفاصيل البيبلوغرافية
| العنوان: |
Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer. |
| المؤلفون: |
Peuker, Kenneth1,2 (AUTHOR), Strigli, Anne1,2 (AUTHOR), Tauriello, Daniele V.F.1,3,4 (AUTHOR), Hendricks, Alexander5,6 (AUTHOR), von Schönfels, Witigo5 (AUTHOR), Burmeister, Greta5,6 (AUTHOR), Brosch, Mario1,2 (AUTHOR), Herrmann, Alexander1,2 (AUTHOR), Krüger, Sandra7 (AUTHOR), Nitsche, Jessica1,2 (AUTHOR), Južnić, Lea1,2 (AUTHOR), Geissler, Marc Marius1,2 (AUTHOR), Hiergeist, Andreas8 (AUTHOR), Gessner, André8 (AUTHOR), Wirbel, Jakob9 (AUTHOR), Ponnudurai, Ruby Priyadarshini9 (AUTHOR), Tunger, Antje10,11 (AUTHOR), Wehner, Rebekka10,11 (AUTHOR), Stange, Daniel E.11,12,13,14 (AUTHOR), Weitz, Jürgen11,12,13,14 (AUTHOR) |
| المصدر: |
Immunity (10747613). Apr2022, Vol. 55 Issue 4, p701-701. 1p. |
| مصطلحات موضوعية: |
*COLORECTAL cancer, *IMMUNE checkpoint inhibitors, *T cells, *MYELOID cells, *IMMUNE checkpoint proteins, *T cell receptors |
| مستخلص: |
Bacterial sensing by intestinal tumor cells contributes to tumor growth through cell-intrinsic activation of the calcineurin-NFAT axis, but the role of this pathway in other intestinal cells remains unclear. Here, we found that myeloid-specific deletion of calcineurin in mice activated protective CD8+ T cell responses and inhibited colorectal cancer (CRC) growth. Microbial sensing by myeloid cells promoted calcineurin- and NFAT-dependent interleukin 6 (IL-6) release, expression of the co-inhibitory molecules B7H3 and B7H4 by tumor cells, and inhibition of CD8+ T cell-dependent anti-tumor immunity. Accordingly, targeting members of this pathway activated protective CD8+ T cell responses and inhibited primary and metastatic CRC growth. B7H3 and B7H4 were expressed by the majority of human primary CRCs and metastases, which was associated with low numbers of tumor-infiltrating CD8+ T cells and poor survival. Therefore, a microbiota-, calcineurin-, and B7H3/B7H4-dependent pathway controls anti-tumor immunity, revealing additional targets for immune checkpoint inhibition in microsatellite-stable CRC. [Display omitted] • Microbial recognition activates myeloid calcineurin and NFAT in colorectal cancer • NFAT-dependent IL-6 promotes expression of co-inhibitory B7H3 and B7H4 by tumors • B7H3/B7H4 inhibit CD8+ T cells while their blockade elicits protective T cell responses • B7H3/B7H4 expression in CRC correlates with poor CD8+ T cell infiltration and survival The mechanisms through which microsatellite-stable colorectal cancer inhibits anti-tumor immunity and resists immune checkpoint blockade are incompletely understood. Peuker et al. describe a microbiota-dependent pathway of crosstalk between myeloid cells, T cells, and tumor cells that inhibits CD8+ T cell-dependent anti-tumor immunity through the co-inhibitory proteins B7H3 and B7H4 and that is amenable to therapeutic targeting. [ABSTRACT FROM AUTHOR] |
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