High CD204⁺ tumor-associated macrophage density predicts a poor prognosis in patients with clear cell renal cell...

Purpose: Tumor-associated macrophages (TAMs) play a crucial role in solid tumors and display varying characteristics depending on the specific tumor microenvironment (TME). The study investigated the presence and characteristics of TAMs in renal clear cell carcinoma (ccRCC) and assessed their influence on patient prognosis. Methods: Immunohistochemistry (IHC) was used to identify CD204⁺ TAMs in a cohort of 72 patients with ccRCC. Kaplan-Meier survival analysis and log-rank test were used to evaluate the prognostic significance of CD204⁺ TAMs in each group. The TCGA-KIRC cohort was used to analyze the relationship between CD204 and immunity. The functions of CD204⁺ TAMs in the TCGA-KIRC cohort were analyzed through GO enrichment analysis. Immunofluorescence (IF) was conducted to confirm the positive effects of CD204 on regulatory T (Treg) cells and exhausted T (Tex) cells. Results: There was a negative relation between high infiltration of CD204⁺ TAMs and both overall survival (OS) and progression-free survival (PFS) in ccRCC. A positive correlation was found between high-infiltrating CD204⁺ TAMs and distant organ metastasis, as well as lymph node metastasis. In the TCGA-KIRC cohort, the group with high expression of CD204 exhibited significant up-regulation of 120 genes as well as enrichment in the negative regulation of immunity. CD204 high-expression group showed up-regulation of Treg cells and Tex cells. Conclusion: The presence of CD204⁺ TAMs in ccRCC is associated with a negative prognosis in patients. The high infiltration of CD204 promotes distant organ metastasis by aggerating Treg cells and Tex cells.