Tumor cells escape anti-tumor immune response in various ways, including functionally shaping the microenvironment through secretion of various chemokines, cytokines, etc. Adenosine is a powerful immunosuppressive metabolite, which is frequently found to be elevated in the extracellular tumor microenvironment (TME). Thus, it has been proposed as a novel antitumor immunoassay to target adenosine generating enzymes such as CD39, CD73, and adenosine receptors in recent years. The discovery of the immune checkpoint such as programmed cell death 1(PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4), have also greatly changed the treatment methods and ideas of malignant tumors. The idea of malignant tumor immunotherapy has been developed from point-to-point therapy targeting immune checkpoint to combine different points of different pathway to create a kind of therapy based on macroscopic immune regulatory system network. This article reviews the theoretical basis of adenosine energy axis and immune checkpoint combined therapy for malignant tumors and the latest advances in malignant tumors.

Objective We performed a retrospective analysis to investigate the clinical characteristics and therapeutic strategies of 20 refractory/recurrent PNH patients, including the clinical efficacy of chemotherapy treatment and survival. Main Measures The clinical data of 20 classic PNH patients that were refractory/recurrent or had glucocorticoid dependence in our hospital were analyzed, including clinical manifestations, laboratory examinations, treatment efficacy and survival. Key Results Seventeen patients had a marked improvement in anemia after chemotherapy, 14 patients acquired blood transfusion independence, and the Hb of 3 patients increased to normal levels. Although 6 patients still needed blood transfusion, the transfusion interval was significantly prolonged. The percentages of LDH, TBIL and RET, which are indicators of hemolysis, were significantly lower than those before chemotherapy. The dosage of adrenal glucocorticoids was reduced by more than half compared with that before chemotherapy. Conclusions Chemotherapy can reduce PNH clones, promote normal hematopoiesis, and control hemolytic attack. It is a promising and widely used therapeutic method.

High expression of the inhibitory receptor programmed death ligand 1 (PD-L1) on the surface of tumor cells have been found play a key role in tumor immune evasion in several human malignancies. However, the expression of PD-L1 on bone marrow mesenchymal stem cells (BMSCs) and whether the PD-1/PD-L1 axis is involved in the BMSCs versus T cell immune response in Multiple Myeloma (MM) remain poorly defined. In this study, we explored the expression of PD-L1 on BMSCs from MM patients and the role of PD-1/PD-L1 pathway in BMSCs-mediated regulation of CD8+T cells. We observed that the expression of PD-L1 on BMSCs was significantly higher in NDMM group, compared with the NC group (18.81±1.61% vs. 2.78±0.70 %; P<0.001). Furthermore, the expression of PD-1 on CD8+ T cells in NDMM group was significantly higher than that in control group (43.22±2.98% vs. 20.71±1.08%; P<0.001). However, there was no significant difference in PD-1 expression of CD4+ T cells and NK cells between NDMM group and NC group. Additionally, the co-culture assays revealed that BMSCs significantly promoted CD8+ T cell apoptosis and suppressed CD8+ T cell function. However, PD-L1 inhibitor effectively reversed BMSCs-mediated suppression in CD8+ T cells. We also found that the combination of PD-L1 inhibitor and pomalidomide can further enhance the killing effect of CD8+ T cells on MM cells. In summary, our findings demonstrated that BMSCs may induce apoptosis and functional imbalance of CD8+ T cells via PD-1/PD-L1 pathway and promote the immunity escape of MM.