Peuker, Kenneth and Strigli, Anne and Tauriello, Daniele V. F. and Hendricks, Alexander and von Schonfels, Witigo and Burmeister, Greta and Brosch, Mario and Herrmann, Alexander and Krueger, Sandra and Nitsche, Jessica and Juznic, Lea and Geissler, Marc Marius and Hiergeist, Andreas and Gessner, Andre and Wirbel, Jakob and Ponnudurai, Ruby Priyadarshini and Tunger, Antje and Wehner, Rebekka and Stange, Daniel E. and Weitz, Juergen and Aust, Daniela E. and Baretton, Gustavo B. and Schmitz, Marc and Rocken, Christoph and Hampe, Jochen and Hinz, Sebastian and Zeller, Georg and Chavakis, Triantafyllos and Schafmayer, Clemens and Batlle, Eduard and Zeissig, Sebastian (2022) Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3-and B7H4-dependent anti-tumor immunity in colorectal cancer. IMMUNITY, 55 (4). 701-+. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | B7 FAMILY-MEMBER; T-CELLS; EXPRESSION ANALYSIS; NUCLEAR FACTOR; MACROPHAGES; SELECTION; PACKAGE; B7-H4; TRANSPLANTATION; INFLAMMATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2023 14:35 |
| Last Modified: | 12 Dec 2023 14:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58746 |
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