CD4 and neoplasm: It was found that tumour-infiltrating PD-L1+ lymphocytes can interact with PD-1+ cells, such as other tumour-infiltrating lymphocytes or macrophages, resulting in bidirectional signalling and immunosuppressive TME, including the inhibition of CD4+ T cells and CD8+ T cells activity, inducing M2 polarization of macrophages and the differentiation of Tregs and Th17, resulting in enhanced secretion of pro-tumourigenic immunosuppressive factors, such as TGF-β, IL-10 and IL-17 [15,16].