Combination treatments with hydroxychloroquine and azithromycin are compatible with the therapeutic induction of anticancer immune responses

羟氯喹和阿奇霉素联合治疗可与抗癌免疫反应的治疗诱导相兼容

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作者:Peng Liu, Liwei Zhao, Gladys Ferrere, Carolina Alves-Costa-Silva, Pierre Ly, Qi Wu, Ai-Ling Tian, Lisa Derosa, Laurence Zitvogel, Oliver Kepp, Guido Kroemer

Abstract

Amid controversial reports that COVID-19 can be treated with a combination of the antimalarial drug hydroxychloroquine (HCQ) and the antibiotic azithromycin (AZI), a clinical trial (ONCOCOVID, NCT04341207) was launched at Gustave Roussy Cancer Campus to investigate the utility of this combination therapy in cancer patients. In this preclinical study, we investigated whether the combination of HCQ+AZI would be compatible with the therapeutic induction of anticancer immune responses. For this, we used doses of HCQ and AZI that affect whole-body physiology (as indicated by a partial blockade in cardiac and hepatic autophagic flux for HCQ and a reduction in body weight for AZI), showing that their combined administration did not interfere with tumor growth control induced by the immunogenic cell death inducer oxaliplatin. Moreover, the HCQ+AZI combination did not affect the capacity of a curative regimen (cisplatin + crizotinib + PD-1 blockade) to eradicate established orthotopic lung cancers in mice. In conclusion, it appears that HCQ+AZI does not interfere with the therapeutic induction of therapeutic anticancer immune responses.

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