| Autor: |
Antonio Di Grazia, Eleonora Franzè, Rachele Frascatani, Federica Laudisi, Teresa Pacifico, Lorenzo Tomassini, Davide Di Fusco, Vincenzo Formica, Giuseppe Sica, Carmine Stolfi, Ivan Monteleone, Giovanni Monteleone |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Experimental Hematology & Oncology, Vol 13, Iss 1, Pp 1-5 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2162-3619 |
| DOI: |
10.1186/s40164-024-00562-y |
| Popis: |
Abstract Interactions between colorectal cancer (CRC) cells and the noncancerous cells in the tumor microenvironment (TME) induce mechanisms for the escape of tumor cells from immune attack. Hepcidin, a peptide that controls immune cell functions, is overproduced by CRC cells. This study aimed to evaluate whether hepcidin acts as a regulator of anti-tumor immunity in CRC. Hepcidin silencing in CRC cells was followed by enhanced TNF-driven caspase-dependent cleavage of GSDM E and death. Mice engrafted with hepcidin-deficient CT26 cells developed fewer and smaller tumors than control mice as a result of the action of tumor-infiltrating CD8+ T lymphocytes and were protected from the development of tumors in a vaccination model and exhibited long-lasting tumor protection. Additionally, hepcidin deficiency enhanced the response of mice bearing CT26-derived tumors to anti-PD-1 therapy. These results suggest that targeting hepcidin in CRC cells enhances the production of TNF thereby triggering a caspase/GSDM E-driven lytic cell death with the downstream effect of boosting a robust immune response against tumor antigens. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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