Figure 9. Schematic representation shows the mechanism through which PBRM1MUT ccRCC cells modulate tumor microenvironment and promote ccRCC progression. The PBRM1 mutant ccRCC cells secrete CCL5 cytokines that promote mast cell recruitment into the TME. The mast cells secrete several factors such as VEGFA, VCAM1, and PDGFA that stimulate angiogenesis. The mast cells also reduce the infiltration of CD8+ T cells and CD4+ T cells. Simultaneously, PBRM1 mutations facilitate tumor cell growth by activating intrinsic HIF signaling pathways. The complex interactions between the mast cells, epithelial cells, T cells, and ccRCC tumor cells in the TME are aided by several cytokines and chemokines that are secreted by these cells regulates tumor progression.