Fig. 2

The synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with other novel therapies. a The co-inhibitory and co-stimulatory pathways regulating the activities of T cells or NK cells. The green circle refers to co-stimulatory pathway, and the red circle refers to co-inhibitory pathway. b Targeted therapy synergizes with α-PD-1/PD-L1. Oncogenic pathways such as MAPK and PI3K-AKT promote PD-L1 transcription. Targeted therapies including EGFR-TKI, ALK-TKI, and RAS inhibitor not only directly retard tumor growth, but also decrease intrinsic PD-L1 expression. Moreover, STING agonist enhances DC function by activating STING-IFN-I pathway. c The bifunctional and bispecific antibody containing α-PD-L1 moiety. The structures of M7824 and YM101. d The effect of gut microbiota on antitumor immunity. Gut microbiota regulates DC function, Th1-skweing immunity, Th17 polarization, Treg differentiation, and cytokines secretion. Altered gut mucosa immunity could influence the effect of systemic anticancer immunotherapy. Abbreviations: EGFR-TKI, epidermal growth factor receptor-tyrosine kinase inhibitor; ALK, anaplastic lymphoma kinase; PARP, Poly (ADP-ribose) polymerase; DSB, double-strand break; STING, stimulator of interferon genes