Causal modulation of lipid metabolism may shape the inflammatory microenvironment and potentially augment immunotherapy: a comprehensive genetic landscape revealed by Mendelian randomization analysis.
Int Immunol
; 36(6): 291-302, 2024 Apr 27.
Article
en En
| MEDLINE
| ID: mdl-38451254
ABSTRACT
Previous observational and experimental studies have suggested a relationship between statin treatments and the augmentation of immunotherapy effects; however, the causal role of statin usage in promoting antitumor immunity remains largely unexplored. Utilizing large-scale genome-wide association studies, we conducted a Mendelian Randomization (MR) analysis to examine the association between genetically proxied inhibition of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a specific target of statins, and 524 immunotherapy-related profiles, encompassing immune cells, inflammatory cytokines, immune checkpoints, and gut microbiota. Our findings indicated a suggestive association between statin therapy and proinflammatory as well as antitumor effects; notably, inhibition of HMGCR demonstrated a robust link with increased susceptibility of various immune cell types, including basophil cells, white blood cells, eosinophil cells, neutrophil cells, activated CD8+ T cells, dendritic cells, and natural killer cells; furthermore, a causal relationship was observed between statin use and a decrease in terminal CD8+ T cells, granulocytes, monocytes, and myeloid-derived suppressor cells; genetically proxied statin usage was also significantly associated with elevated levels of proinflammatory cytokines and immunotherapy-related gut microbiota; importantly, the potential inhibition of HMGCR in influencing the response to immunotherapy was confirmed in the real-world cohorts. This study provides novel insights into the regulatory role of HMGCR inhibition in antitumor immunity, suggesting that strategies targeting HMGCR or lipid regulation may hold therapeutic potential for enhancing the efficacy of immunotherapy.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Metabolismo de los Lípidos
/
Análisis de la Aleatorización Mendeliana
/
Inmunoterapia
Límite:
Humans
Idioma:
En
Revista:
Int Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China