Auranofin and the efficacy of anti-PD1 immunotherapy.

person Yan Zhang Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China info_outline Yan Zhang

Authors person Yan Zhang Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China info_outline Yan Zhang Organizations Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, China Abstract Disclosures Research Funding No funding received None. Background: Anti-PD-1 immunotherapy brings hope for the treatment of malignant tumors, but its overall response rate is low.Therefore, how to sensitize anti-PD-1 therapy to make more patients benefit from immunotherapy is an urgent clinical demand. Methods: PKCι, as a classical oncogenic gene that affects cell proliferation and differentiation, has recently been found to participate in the formation of tumor immunosuppressive microenvironment (TIME). TIME directly leads to resistance to anti-PD1 therapy, so by inhibiting the expression of PKCι to regulate the inhibitory tumor immune microenvironment and sensitize anti-PD1 therapy. Auranofin is a commonly used anti-inflammatory drug in clinic. Recently, it was found that it can inhibit the expression of PKCι and retard growth of tumor. Results: Our study found that interference with PKCι expression in tumor cells can reverse the immunosuppressive microenvironment and enhance the effect of anti-PD1 therapy. Auranofin (PKCι inhibitor) combined with anti-PD-1 immunotherapy has better anti-tumor effect than single drug therapy. Auranofin can inhibit the expression of PKCι and its downstream YAP1 and TNFα, reduce the recruitment of immunosuppressive cells such as MDSCs and Treg, promote the infiltration of effector T cells, ultimately reverse the inhibitory immune microenvironment and play a synergistic anti-tumor role. Conclusions: In summary, the combination of Auranofin and anti-PD-1 immunotherapy can reverse the TIME to sensitize the immune effect, play a synergistic anti-tumor effect, and provide a new idea and theoretical basis for immunotherapy of malignant tumors.