Figure 3.

Activation of the CS in an RCC microenvironment. The first step is represented by C1q TAM secretion that contributes to pro-tumoral TAM phenotypes, T cell exhaustion, adhesion of tumor cells to the extracellular matrix, and neoangiogenesis. RCC cancer cells produce C1r and C1s, leading to an active C1 complex formation. This, in association with IgG deposits on tumor cells, promotes the classical pathway of the CS. Tumor cells also secrete the subsequent complement components, leading to C4 and C3 activation fragment deposition (C4b, C4d and C3b, iC3b, C3d). Moreover, anaphylatoxins C3a and C5a produced by the activation of the classical pathway modulate tumor cells and TME. Abbreviations: TAMs, tumor-associated macrophages; mDCs, myeloid dendritic cells.