Fig. 2
Potential antitumor immune mechanisms induced by intestinal dysbiosis. a In the presence of intact mucosal barrier and signals from commensal microbiota, effector T cell activation is modulated by T cell receptor (TCR) ligation with major histocompatibility complex (MHC) class I, and co-stimulation of CD80/CD86 and CD28. Binding of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) receptor to anti-CTLA-4 antibody on Treg impairs its effector T-cell inhibitory function. It also downregulates CTLA-4 expression on APC. Ligation of repressive receptor programmed death receptor 1 (PD-1) and its ligand PD-L1 to anti-PD-1 and anti-PD-L1 antibodies, respectively, activate effector T-cell proliferation and function. Activated effector T cells interact with tumor cells and release cytokines to induce tumor cell death. b Signals from unfavorable microbes due to dysbiosis upregulates CTLA-4, PD-1 and PD-L1 expression to inhibit T-cell activation. CTLA-4 on Treg binds to CD80/CD86 on antigen presenting cell (APC). CD80/CD86 on APC also dis-engages from CD28 and binds to CTLA-4 on effector T cells. PD-L1, the ligand of PD-1, is expressed on antigen presenting cell (APC) and tumor cells. PD-1 on effector T cells ligates to PD-L1 on APC and tumor cells. These activities inhibit effector T-cell activation, reduces immune checkpoint inhibitor (ICI) efficacy, and causes tumor escape