Fig. 2
From: Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy
Mechanisms of inhibition of T cell activation induced by CTLA-4 and PD-1. Tumor cells or antigen-presenting cells transmit stimulatory and inhibitory signals to modulate T cell activation. The T cell receptor (TCR) interacts with the major histocompatibility complex (MHC)-peptide complex presented by antigen-presenting cells (APCs). CD28-CD80/CD86 interaction induced costimulatory signaling promotes T cell activation. Cytotoxic T lymphocyte antigen 4 (CTL A-4) decreases CD28 signaling by competing for the shared ligands (CD80/CD86). The CTLA-4-CD80/CD86 interaction induces inhibitory signaling by protein phosphatase 2A (PP2A) or Src homology 2 domain-containing phosphatase 2 (SHP2). Upon the binding of programmed cell death 1 (PD-1) with programmed cell death 1 ligand 1 (PD-L1)/programmed cell death 1 ligand 1 (PD-L2), the immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM) motifs in PD-1 are phosphorylated, resulting in the recruitment of phosphatases SHP1 and SHP2. This activity leads to the dephosphorylation of key molecules in the TCR and CD28 signaling pathways, thereby inhibiting T cell activation