New Research Reveals The Reason That Tumor Cells Will Lead to Immunotherapy Resistance

It is well known that the immune system can recognize and eliminate cancerous cells in the body under normal circumstances, but during tumor development, tumor cells will also inhibit the immune system through different strategies, and can not play a role in killing tumor cells. In recent years, immunological checkpoint inhibitors have brought new hopes for cancer patients, but the high resistance to drugs still hampers the application of drugs. In order to overcome this problem, 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 the international academic journal Cancer Discovery.

In this study, the researchers observed that tumors treated with PD-1/PD-L1 blocking antibodies were resistant to antibodies by up-regulation of CD38, and all-trans retinoic acid and IFN-? in the tumor microenvironment can induce CD38 expression. In vitro and in vivo studies have demonstrated that CD38 inhibits the function of CD8+ T cells via the adenylate receptor signaling pathway, blocking the role of CD38 or adenylate receptors is an effective way to overcome the tumor's inhibition of PD-1/PD-L1 blocking antibodies.

In addition, the researchers also conducted a large dataset study of human tumors. Immunological checkpoint inhibitors are most effective in the treatment of high-level T-cell infiltrating tumors, however, the results indicate that CD38 expression is also present in tumors with high levels of T cell infiltration. This study reveals a new mechanism by which tumors are resistant to immunological checkpoint inhibitors, providing new opportunities to improve the efficacy of this treatment in cancer treatment.

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