VISTA deficiency exerts anti-tumor effects in breast cancer through regulating macrophage polarization.

Autor: Jin S; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China., Liu W; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China., He X; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China., Zhang Y; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China., Chen W; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China., Wu Y; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China., Liu J; New Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China. Electronic address: junliu@cpu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Jul 30; Vol. 136, pp. 112365. Date of Electronic Publication: 2024 May 30.
DOI: 10.1016/j.intimp.2024.112365
Abstrakt: Growing evidence had showed that tumor-associated macrophages (TAMs) have a tumor-promoting M2 phenotype which could drive pathological phenomena. In breast cancer, TAMs are abundantly present and may play an important role in the development of breast cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory checkpoint and immunotherapy target for tumor through regulating immune response. However, its effects on macrophages have not been investigated, which was also the focus of this study. Here, the scRNA-seq data further revealed that VISTA was highly expressed in multiple macrophage subclusters. In vitro experiments showed that the absence of VISTA enhanced the M1 polarization of macrophages, inhibited the M2 polarization of macrophages and the proliferation and phagocytosis of 4 T1 cells induced by M2-CM. VISTA regulated the activation of STAT1 and STAT6 signaling pathways in the process of macrophage polarization. In vivo experiments demonstrated that VISTA deficient mice exhibited reduced tumor growth, possibly due to the increase of M1 macrophages and the decrease of M2 macrophages. In summary, our study is the first to reveal the effect of VISTA on macrophages in breast cancer, which showed that VISTA affects tumor growth by critically regulating the macrophage polarization through the STAT pathway.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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