It is well known that the immune system can recognize and remove cancerous cells under normal conditions, but tumor cells will inhibit the immune system in the tumor development process, through different strategies so that the immune system cannot exert its killing effect on tumor cells. In recent years, although immunological checkpoint inhibitors have brought new hopes for cancer patients, the high resistance to drugs still hampers the drug use. Therefore, it is necessary to conduct in-depth research on the mechanism of resistance.


Recently, researchers from the MD Anderson Cancer Center in the United States have found that CD38 can cause tumor cells to resist immune checkpoint inhibitors and further reveal the mechanism. The relevant research results were published in Cancer Discovery.

In this study, the researchers observed that tumors treated with PD-1/PD-L1 blocking antibody were resistant to antibodies by up-regulation of CD38, and all-trans retinoic acid and IFN-β in the tumor microenvironment could induce the expression of CD38. In vitro and in vivo studies have demonstrated that CD38 inhibits the function of CD8+ T cells via the adenylate receptor signaling pathway and blocking the CD38 or adenylate receptors is an effective method to get over the inhibition of PD-1/PD-L1 blocking antibodies by tumors.

In addition, the researchers also conducted a large dataset study of human tumors. Immunological checkpoint inhibitors are the most effective in the treatment of high-level T-cell infiltrating tumors, but the results indicate that CD38 are also expressed in tumors with high levels of T-cell infiltration.

In summary, this study reveals a new mechanism by which tumors are resistant to immunological checkpoint inhibitors, providing new opportunities to improve the efficacy of the cancer treatment.

Reference: Limo Chen, et al. CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Cancer Discovery, DOI: 10.1158/2159-8290.CD-17-1033