Concomitant NAFLD Facilitates Liver Metastases and PD-1-Refractory by Recruiting MDSCs via CXCL5/CXCR2 in Colorectal Cancer.
Cell Mol Gastroenterol Hepatol
; 18(2): 101351, 2024.
Article
en En
| MEDLINE
| ID: mdl-38724007
ABSTRACT
BACKGROUND & AIMS:
Both nonalcoholic fatty liver disease (NAFLD) and colorectal cancer (CRC) are prevalent worldwide. The effects of concomitant NAFLD on the risk of colorectal liver metastasis (CRLM) and its mechanisms have not been definitively elucidated.METHODS:
We observed the effect of concomitant NAFLD on CRLM in the mouse model and explored the underlying mechanisms of specific myeloid-derived suppressor cells (MDSCs) recruitment and then tested the therapeutic application based on the mechanisms. Finally we validated our findings in the clinical samples.RESULTS:
Here we prove that in different mouse models, NAFLD induces F4/80+ Kupffer cells to secret chemokine CXCL5 and then recruits CXCR2+ MDSCs to promote the growth of CRLM. CRLM with NAFLD background is refractory to the anti-PD-1 monoclonal antibody treatment, but when combined with Reparixin, an inhibitor of CXCR1/2, dual therapy cures the established CRLM in mice with NAFLD. Our clinical studies also indicate that fatty liver diseases increase the infiltration of CXCR2+ MDSCs, as well as the hazard of liver metastases in CRC patients.CONCLUSIONS:
Collectively, our findings highlight the significance of selective CXCR2+/CD11b+/Gr-1+ subset myeloid cells in favoring the development of CRLM with NAFLD background and identify a pharmaceutical medicine that is already available for the clinical trials and potential treatment.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Receptores de Interleucina-8B
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Modelos Animales de Enfermedad
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Quimiocina CXCL5
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Receptor de Muerte Celular Programada 1
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Enfermedad del Hígado Graso no Alcohólico
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Células Supresoras de Origen Mieloide
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Neoplasias Hepáticas
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Cell Mol Gastroenterol Hepatol
/
Cell Mol. Gastroenterol. Hepatol
/
Cellular and molecular gastroenterology and hepatology
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos