Fig. 2

Activation and deactivation of CD8⁺ T cells

Dendritic cells (DCs), natural killer (NK) cells, and CD4+ T cells play significant roles in the activation of CD8⁺ T cells. DCs interact with CD8⁺ T lymphocytes via receptor ligands. CD4⁺ T cells facilitates the activation of CD8⁺ T cells by stimulating them. DCs promote the development of CD4⁺ T cells into antigenspecific effector T cells. CD4⁺ T cells stimulate CD8⁺ T cell start via cytokines. CD4⁺ T cells can also contribute to DC activation and licensing by inducing DC maturation, co-stimulatory molecule expression, and cytokine secretion, all of which activate CD8⁺ T cells. NK cells also perform similar functions. In the effector stage, CTLs are activated to kill target cells by granule cytotoxicity and Fas ligand (FasL)-mediated apoptosis. CTLs emit IFN-γ and TNF-α, causing cytotoxicity in cancer cells. NK cells play similar functions. In the immunosuppressive phase, activated CTLs are activated and licensed to express co-stimulatory molecules and secrete cytokines. In the immunosuppressive stage, activated T cells begin to express co-inhibitory receptors, such as the programmed death-1 receptor (PD-1), within hours or days of activation. This occurs through IFN-γ induction of programmed death- 1 ligand (PD-L1) expression in anti-tumor M1 macrophages and cancer cells. Expression of CTL-associated antigen 4 (CTLA-4) by regulatory T cells (Tregs) can also inhibit the suppressive activity of CD8⁺ T cells, thereby triggering immunosuppressive activity within the TME