Heterogeneous Expression of TREM2 And STAB1 Among Tumor-Associated Macrophages in Clear-Cell Renal Cell Carcinoma.

Abstract

Tumor-associated macrophages (TAMs) play important roles in shaping the tumor microenvironment and regulating antitumor immune responses. Triggering receptor expressed on myeloid cells 2 (TREM2) and stabilin-1 (STAB1/CLEVER1) have recently attracted attention as molecules associated with immunosuppressive macrophage phenotypes; however, their expression patterns in clear-cell renal cell carcinoma (ccRCC) remain unclear. This study aimed to examine TREM2 and STAB1 expression in ccRCC using public transcriptomic datasets and public single-cell RNA sequencing data, as well as immunohistochemistry using ccRCC specimens. In the TCGA cohort, high TREM2 and STAB1 mRNA expression was associated with poor overall survival and advanced tumor stage. In an independent immunohistochemistry cohort, TREM2 was expressed mainly in TAMs, whereas STAB1 was expressed in both TAMs and endothelial cells. TREM2-positive TAM density was significantly associated with high nuclear grade, whereas STAB1-positive TAM density was not. Double immunohistochemistry and single-cell RNA sequencing analyses suggested different, but partially overlapping, expression patterns of TREM2 and STAB1 among TAMs. TREM2-high TAMs showed features of monocyte-derived macrophages, whereas STAB1-high TAMs showed features associated with tissue-resident macrophages. These findings suggest that TREM2-positive TAMs and STAB1-positive TAMs contribute differently to the immune microenvironment of ccRCC. Further studies are needed to clarify their functional significance and therapeutic potential.