MARCO+ Tumor-Associated Macrophages Impede CD8+ T Cell Immunity to Facilitate Immunotherapy Resistance in Renal Cell Carcinoma.

ABSTRACT: Immune checkpoint blockade (ICB) therapy, especially in combination regimens, has significantly increased survival of renal cell carcinoma (RCC) patients. However, the ICB-resistant mechanisms remain largely unclear and require further investigation. Here, an immunosuppressive ecosystem in ICB-resistant tumors is identified, featured by preferential infiltration of MARCO+ tumor-associated macrophages (TAMs) and restrained cytotoxicity of CD8+ cytotoxic T lymphocytes (CTLs). The infiltrated MARCO+ TAMs can obstruct the development of CD8+ CTLs by impairing MHC-I-mediated neoantigen cross-presentation. Mechanistically, MARCO up-regulates the expression of SOCS1, which obstructs the kinase activity of JAK1, thereby downregulating MHC-I expression through the inhibition of the JAK1-STAT1-NLRC5

SUBMITTER: Chen J 

PROVIDER: S-EPMC12713061 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature