In clear-cell renal cell carcinoma, tumour-associated macrophages generate C1r, C1s, C4, and C3, after being hijacked by cancer cells, and then initiates the classical pathway of the complement cascade of IgG immunity in tumour and promotes inflammation and T-cell exhaustion, leading to tumour progression (Roumenina et al., 2019b). The gene discussed is C4A; the disease is cancer.