Phenotypic differences in tumor-associated macrophages between metastatic and primary sites of clear cell renal cell carcinoma.

Abstract

105 Background: Tumor-associated macrophages (TAMs) are one of the key contributors to the tumor microenvironment and are phenotypically differentiated into M1 and M2 macrophages. M1 macrophages stimulate anti-tumor immune responses, whereas M2 macrophages promote immunosuppression and are associated with tumor progression in clear cell renal cell carcinoma (ccRCC). However, little information is available regarding the difference in TAM polarization between primary and metastatic lesions of ccRCC. Methods: We collected paired samples of primary and matched metastatic sites from the first recurrence in 41 metastatic ccRCC patients. Immunohistochemistry (IHC) for Iba1, which is a common pan-macrophage marker, and CD163 and CD204, which are considered to be M2 macrophage markers, was performed on all paired samples. Results: Thirty-three paired primary and metastatic samples were available for IHC assessment in this analysis. The most common metastatic sites were lung (N = 26, 78.8 %) and lymph node (N = 3, 9.1 %). The mean (± standard deviation) cell density of Iba1+ TAMs was higher in metastatic lesions than in primary lesions (756 ± 267 mm2 vs. 581 ± 155 mm2, P = 0.0012). By contrast, the ratio of CD163+ and CD204+ to Iba1+ TAMs was significantly lower in metastatic lesions than in primary lesions (0.76 ± 0.30 vs. 0.90 ± 0.24, P = 0.0067 and 0.39 ± 0.27 vs. 0.67 ± 0.29, P = 0.0001, respectively). The median overall survival of patients with high- vs. low-density Iba1+, CD163+, and CD204+ TAMs in metastatic lesions was 120 vs. 92 months (log-rank P = 0.67), 120 vs. 58 months (log-rank P = 0.056), and 120 vs. 92 months (log-rank P = 0.35), respectively. Conclusions: TAMs in the metastatic lesions of ccRCC polarized towards an M1-like phenotype, although the total number of TAMs was greater in metastatic compared with primary lesions. The cell density of Iba1+, CD163+, and CD204+ TAMs in metastatic sites was not associated with overall survival in patients with ccRCC.