B7-H3 but not PD-L1 is involved in the antitumor effects of Dihydroartemisinin in non-small cell lung cancer

Dihydroartemisinin (DHA), an active antimalaria metabolite derived from artemisinin, has received increasing attention for its anticancer activities. However, little is known about the anticancer mechanisms of DHA, although the existing data define its antimalaria effects by producing excessive reactive oxygen species (ROS). In this study, we showed that DHA effectively suppresses in vitro and in vivo tumor growth of non-small cell lung cancer (NSCLC) without perceptible toxicity on heart, liver, spleen, lung, and kidney tissues. Of note, DHA inhibited the expression of B7-H3 rather than PD-L1, whereas overexpression of B7-H3 completely rescued DHA's inhibition on cell proliferation and migration of NSCLC A549 and HCC827 cells. B7-H3 overexpression also largely inhibited DHA's induction on the apoptosis of the two cell lines. Furthermore, DHA treatment led to increased infiltration of CD8+ T Lymphocytes in the xenografts as compared with that of negative controls. Taken together, our results suggest that B7-H3 but not PD-L1 is involved in the antitumor effects of DHA in NSCLC, which may be indicative of an effective B7-H3 blockade and further combination with anti-PD-L1/PD-1 immunotherapy. •Dihydroartemisinin (DHA) inhibits Non-small cell lung cancer (NSCLC) growth.•B7-H3 instead of Programmed death ligand 1 (PD-L1) is downregulated in NSCLC by DHA.•Overexpression of B7-H3 rescues DHA's inhibition on NSCLC.•DHA administration increases intratumoral CD8+ lymphocyte infiltration.