Immunotherapy has achieved great success recently and opened a new avenue for anti-tumor treatment. Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) are typical immune checkpoints that transmit coinhibitory signals, muting the host immunity. Monoclonal antibodies that block PD-1/PD-L1 axis have benefited many patients with different tumor diseases. However, the objective response rate is still unsatisfactory. In this review, we summarize three strategies targeting PD-L1 based on different forms of PD-L1 and various regulating mechanisms to enhance the therapeutic effect, including blockade of the interaction between PD-L1 and PD-1, downregulation of PD-L1 expression and degradation of mature PD-L1. Thereinto, we describe a variety of materials have been designed to target PD-L1, including antibodies, nanoparticle, peptide, aptamer, RNA, and small molecule. Additionally, we list the drugs with PD-L1 regulation capacity used in clinical and ongoing studies to explore other alternatives for targeting PD-L1 besides anti-PD-L1 monoclonal antibodies. Moreover, we discuss associated opportunities for cancer combination therapy with other modalities such as chemotherapy, radiotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT), as these conventional or emerging modalities are capable of increasing the immune response of tumor cells by altering the tumor microenvironment (TME), and would display synergistic effect. At last, we give a brief summary and outlook regarding the research status and future prospect of immunotherapy.

Recent findings indicate that bone marrow mesenchymal stem cells (BMSCs) participate in the process of neovascularization in response to repair to injury and are involved in postinfarction myocardial repair. It is unclear what special characteristics the vascular progenitors of bone marrow origin has. CXCR4(+) stem/progenitor cells mobilized to the infarct area and improved the myocardial repair. In present study, we aimed to determine whether CXCR4(+)BMSCs contribute to the angiogenic capacity in vitro and in vivo. CXCR4(+)BMSCs were separated by using paramagnetic microbeads and cultured. RT-PCR and FACS analysis confirmed the gene expression phenotype. The uptake of acetylated low density lipoprotein (acLDL) and the tube formation evaluated the function of CXCR4(+)BMSCs. The effect of CXCR4(+)BMSCs transplantation on neovascularization was investigated in a murine model hindlimb ischemia. After induced by VEGF, CXCR4(+)BMSCs expressed the endothelial cells (ECs) phenotype. The expression of EC markers, PECAM-1, and von Willebrand factor (vWF) increased significantly at both the mRNA and protein levels. In addition, CXCR4(+)BMSCs enhanced the uptakes of Dil-acLDL and form capillary-like tubes in vitro. In vivo the local transfer of CXCR4(+)BMSCs increased neovascularization in ischemic hindlimb. These results demonstrate that CXCR4(+)BMSCs differentiate into ECs and contribute to neovascularization in the vascular lesion,, which indicate the important therapeutic implications for cardiovascular diseases and a new cell source for cell-based vascular engineering and repair in the future.