Immune microenvironment in clear cell type renal cell carcinoma with loss of PBRM1 protein expression

Abstract

Abstract Background Polybromo-1 (PBRM1) is a chromatin-modifying gene and its mutation is detected in approximately 40% of clear cell type renal cell carcinoma (ccRCC). It has been recently reported that PBRM1 mutation was positively associated with the efficacy of immune checkpoint inhibitors. Previously, our group demonstrated the tumor heterogeneity of PBRM1 and tumor associated macrophages (TAMs) differentiation between primary and metastatic site of ccRCC, separately. Here, we evaluated the relationship between the protein expression of PBRM1 in tumor cells and their immune microenvironment. Methods We performed immunohistochemistry (IHC) for PBRM1, CD8, Iba1, which is a common pan-macrophage marker, CD163 and CD204, which are considered to be a M2 macrophage marker using tissue microarray samples of both primary and matched metastatic sites in 41 metastatic ccRCC patients. Results Thirty-three paired samples were available for IHC assessment. The density of CD8+ T cells was significantly lower in PBRM1 protein expression-negative tumor than -positive tumor (average ± standard error [SE] density in PBRM1-positive vs. -negative tumor was 367 ± 94/m2 vs. 650 ± 71/m2, P = 0.023) in metastatic site. The density of CD163+ TAMs was significantly higher in PBRM1 protein expression-negative tumor than -positive tumor (average ± standard error [SE] density in PBRM1-positive vs. -negative tumor was 693 ± 74/m2 vs. 471 ± 56/m2, P = 0.023) in metastatic site. By the contrast, no significant relationship between PBRM1 protein expression and the density of CD8+ T cells or TAM was observed in primary site. Conclusion TAMs were polarized towards an M2-like phenotype and CD8+ T cells density decreased in metastatic lesion of PBRM1 protein expression-negative ccRCC. Further investigation with large sample size is warranted.