Department of Microbiology and Immunology, Innovative Therapeutics Research Institute, Inje University College of Medicine, Republic of Korea.
Department of Obstetrics and Gynecology, Republic of Korea; Paik Institute for Clinical Research, Busan, Republic of Korea.
Biochem Biophys Res Commun. 2022 Nov 5;628:18-24. doi: 10.1016/j.bbrc.2022.08.055. Epub 2022 Aug 24.
VSIG4, a newly identified co-inhibitory molecule belonging to the B7-related family, is exclusively expressed on tissue-resident macrophages and is involved in the suppression of T cell proliferation and cytokine production. We sought to characterize the role of VSIG4 in anti-tumor immunity in the tumor microenvironment, focusing on VSIG4-expressing tumor-associated macrophages (TAMs). We found that VSIG4-expressing TAMs negatively regulated antigen-specific T cell proliferation and cytokine production through direct inhibition via cell cycle arrest, but not apoptosis, as well as through their arginase 1 activity. Furthermore, VSIG4-expressing TAMs suppress tumor-specific CD8 T cell cytotoxicity. Therefore, our results suggest that VSIG4-expressing TAMs could be a negative cellular regulator of anti-tumor immunity in the tumor microenvironment.
VSIG4 是一种新鉴定的共抑制分子，属于 B7 相关家族，它仅在组织驻留巨噬细胞上表达，并参与抑制 T 细胞增殖和细胞因子产生。我们试图研究 VSIG4 在肿瘤微环境中的抗肿瘤免疫中的作用，重点是 VSIG4 表达的肿瘤相关巨噬细胞（TAMs）。我们发现 VSIG4 表达的 TAMs 通过细胞周期停滞而不是细胞凋亡直接抑制，通过其精氨酸酶 1 活性，负调控抗原特异性 T 细胞增殖和细胞因子产生。此外，VSIG4 表达的 TAMs 抑制肿瘤特异性 CD8 T 细胞细胞毒性。因此，我们的结果表明，VSIG4 表达的 TAMs 可能是肿瘤微环境中抗肿瘤免疫的负性细胞调节剂。
