腫瘍免疫を二分する特異なマクロファージの同定～がん細胞が免疫を低下させる仕組み～

2025-06-16 理化学研究所

がん細胞膜を獲得した抑制系腫瘍関連マクロファージ

<関連情報>

• https://www.riken.jp/press/2025/20250616_1/index.html
• https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00571-6

腫瘍免疫の分岐を決定する異種交配能を持つTAMサブセット Distinct TAM subset with cross-dressing capability determines the bifurcation of tumor immunity

Kanako Shimizu ∙ An Sanpei ∙ Hiroshi Nakazato ∙ … ∙ Satoru Yamasaki ∙ Jun Nakabayashi ∙ Shin-ichiro Fujii
Cell Reports  Published:June 8, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.115800

Highlights

• CD9⁺CD63⁺TAMs close to tumor cells can cross-dress via trogocytosis
• CH25H is a key regulator of TAM trogocytosis in TEM
• IFN-β increases CH25H expression and suppresses TAM trogocytosis
• VHL upregulates CH25H, while HIF-1α downregulates CH25H, modulating TAM function

Summary

Tumor-associated macrophage (TAM) heterogeneity significantly influences the tumor microenvironment, positioning TAM inhibition as a promising anticancer strategy. Although several TAM subsets have been described, their functional roles remain unclear. In this study, we identified a distinct subset of CD9^hiCD63^hiCD206⁺Class II^lo hypoxic TAMs, located near tumors. These TAMs engage in trogocytosis, acquiring tumor membrane fragments, and cross-dress major histocompatibility complex (MHC)/tumor antigen epitopes. These processes facilitate their recognition by cytotoxic T lymphocytes, enhancing antitumor immune responses. We further found CH25H as a key regulator of TAM cross-dressing, with its inhibition associated with the activity of HIF1-α and VHL. These findings highlight the potential of modulating TAMs as an innovative immunotherapy strategy.