CD8A and neoplasm: In 2009, on the basis of the density of CD3+ and CD8+ T-cells at the tumor center (TC) and invasive margin (IM), four types of TIME models were first proposed [21]: cold tumors (low levels of CD3+/CD8+ at both TC and IM), altered excluded tumors (high levels of CD3+/CD8+ at IM but very little at TC), altered immunosuppressive tumors (low levels of CD3+/CD8+ at IM and TC), and hot tumors (high levels of CD3+/CD8+ at both TC and IM).