Fig. 1

The synergistic antitumor efficacies and mechanisms of α-PD-1/PD-L1 in combination with chemotherapy, radiotherapy, or angiogenesis inhibitor. a Chemotherapy synergizes with α-PD-1/PD-L1. Some cytotoxic chemotherapeutic drugs could induce immunogenic cell death and stimulate antitumor immune response. Immunogenic cell death is featured with some upregulated damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), ATP, and high-mobility group box 1 (HMGB1). The ATP-P2RX7, CRT-CD91, and HMGB1-TLR4 pathways facilitate the antigen capture and presentation of DC, ultimately motivating adaptive antitumor immune response. Apart from immunogenic cell death, low-dose chemotherapy depletes regulatory T cells (Tregs) and promotes the repolarization of tumor-associated macrophage (TAM) from M2-like to M1-like phenotype. b Radiotherapy synergizes with α-PD-1/PD-L1. Firstly, radiotherapy could induce immunogenic cell death, enhance antitumor immune response, promote T cell infiltration, expand T-cell receptor (TCR) repertoire in the TME. Secondly, radiotherapy upregulates the expression of PD-L1 on tumor cells, which might be utilized by additional α-PD-1/PD-L1. Thirdly, radiotherapy increases the MHC-I on tumor cells and relieves resistance to α-PD-1/PD-L1. c Angiogenesis inhibitor synergizes with α-PD-1/PD-L1. Angiogenesis inhibitor blocks proangiogenic pathways, promotes vessel normalization, improves tumor perfusion and oxygenation, restores the hypoxic TME, and enhances drug delivery. Also, angiogenesis inhibitor reshapes the TME: promoting T cell infiltration and DC maturation, enhancing the differentiation towards M1-like macrophage, decreasing the ratio of Treg and MDSC, and alleviating hypoxia-induced PD-L1