Figure 2.

Schematic representation of TIME (Tumor Immune MicroEnvironment) classification. (a) The PD-1/PD-L1 pathway represents an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous immune anti-tumor activity. Engagement of PD-L1 expressed on the tumor cells to PD-1 receptors on the activated T cells leads to inhibition of cytotoxic T cells. (b1–b4) Classification into 4 subtypes listed as TIME. (b1) PD-L1-, TIL− is classified into type 1 (T1). (b2) PD-L1+, TIL+, belongs to type 2 (T2). (b3) PD-L1−, TIL+ belongs to type 3 (T3) and (b4) PD-L1+, TIL−, classified as type 4 (T4) although its existence is under debate. MHC: major histocompatibility complex. TCR: T cell receptor. TAAs: tumor-associated antigens. TSAs: tumor-specific antigens. Legends at the top right.