摘要：SummaryHydroxychloroquine (HCQ) is a well-known anti-inflammatory drug but is also known as an anti-inflammatory drug. Here, we evaluate the influence of HCQ treatment on the effect of anti-PD1 tumor immunotherapy. Anti-PD1 therapy-sensitive tumor lines MC38, CT26, and RIL-175 were used to investigate the impact of HCQ on anti-PD1 therapy efficacy.In vitroassays demonstrated that HCQ directly inhibited tumor cell growth in all the tested tumor cell lines. HCQ treatment impaired both antigen-specific and nonspecific T-cell production of TNFα and IFNγin vitroandin vivo. Importantly, in all the three tumor models, HCQ treatment significantly impaired the response to anti-PD1 treatment, accompanying diminishedin vivoT-cell activation and reduced tumor-infiltrating, antigen-specific CD8+T cells. This study shows that HCQ treatment can result in immunotherapy failure due to its immunosuppressive effects that offset both increased MHC-I expression by tumor cell and direct cytotoxicity.Graphical abstractDisplay OmittedHighlights•HCQ inhibits both antigen-specific and nonspecific CD4+and CD8+T function•HCQ inhibits tumor cell growthin vitro•HCQ impairs anti-PD1 therapyCancer; Immunology
