Lactate drives the ESM1-SCD1 axis to inhibit the antitumor CD8+ T-cell response by activating the Wnt/ß-catenin pathway in ovarian cancer cells and inducing cisplatin resistance.
Int Immunopharmacol
; 137: 112461, 2024 Aug 20.
Article
en En
| MEDLINE
| ID: mdl-38897128
ABSTRACT
Ovarian cancer (OC) is a gynecological malignancy that results in a global threat to women's lives. Lactic acid, a key metabolite produced from the glycolytic metabolism of glucose molecules, is correlated with tumor immune infiltration and platinum resistance. In our previous study, we found that endothelial cell-specific molecule 1 (ESM1) plays a key role in OC progression. This study revealed that lactate could upregulate ESM1, which enhances SCD1 to attenuate the antitumor CD8+ T-cell response. ESM1 and SCD1 expression levels were significantly greater in OC patients with high lactic acid levels than in those with low lactic acid levels. Further mechanistic studies suggested that the Wnt/ß-catenin pathway was inactivated after ESM1 knockdown and rescued by SCD1 overexpression. IC50 analysis indicated that the ESM1-SCD1 axis induces the resistance of OC cells to platinum agents, including cisplatin, carboplatin, and oxaliplatin, by upregulating P-gp. In conclusion, our study indicated that the induction of SCD1 by lactic acid-induced ESM1 can impede the CD8+ T-cell response against tumors and promote resistance to cisplatin by activating the Wnt/ß-catenin pathway in ovarian cancer. Consequently, targeting ESM1 may have considerable therapeutic potential for modulating the tumor immune microenvironment and enhancing drug sensitivity in OC patients.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Proteoglicanos
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Cisplatino
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Linfocitos T CD8-positivos
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Resistencia a Antineoplásicos
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Ácido Láctico
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Vía de Señalización Wnt
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Proteínas de Neoplasias
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Antineoplásicos
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
/
Int. immunopharmacol
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International immunopharmacology
Asunto de la revista:
ALERGIA E IMUNOLOGIA
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FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China