CD4 and neoplasm: Immune-inflamed is characterized by the presence of CD8+ and CD4+ T cells in the tumor parenchyma accompanied by the expression of immune checkpoint molecules [75], indicating a potential anti-tumor immune response to ICIs treatment [73]; immune-excluded is characterized by the presence of different immune cell types in the aggressive margin or stroma of tumor, but cannot infiltration into tumor parenchyma [74, 76].