Artemisinin improves the efficiency of anti-PD-L1 therapy in T-cell lymphoma

Abstract

Abstract Although immune checkpoint inhibitors targeting PD-1/PD-L1 pathway have obtained favorable results in T-cell lymphoma clinical trials, the majority of T-cell lymphoma patients appear to be minimally sensitive to PD-1/PD-L1 blockade. The malaria drug artemisinin has previously been identified as a potent anti-lymphoma drug and was tested as a combination treatment with anti-PD-L1 antibody in T-cell lymphoma. In this study, we found that artemisinin caused ferroptosis by up-regulating ROS levels and increasing misfolded protein in T-cell lymphoma via down-regulating ERK pathway. As expected, artemisinin or anti-PD-L1 monoclonal antibody therapy alone could inhibit EL4 T-cell lymphoma growth in Balb/c nude mice. Interestingly, combination therapy with artemisinin greatly improved the anti-lymphoma efficiency of anti-PD-L1 monoclonal antibody. These results provide further rationale for the combination therapy of artemisinin with anti-PD-L1 antibody in preclinical settings. This work was supported by the National Natural Science Foundation of China (Grant 81501356 and Grant 81373112), the Shenzhen Basic Science Research Project (Grants JCYJ20170413153158716 and JCYJ20170818164619194), Nanshan pilot team project (LHTD20160004), Start-up funding (CYZZ20180307154657923), Guangdong Provincial Research Award for Thousand Talents Program Scholars.