Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+cells elimination in hepatocellular carcinoma
摘要Cryoablation(CRA)and microwave ablation(MWA)are two main local treatments for he-patocellular carcinoma(HCC).However,which one is more curative and suitable for combining with immunotherapy is still controversial.Herein,CRA induced higher tumoral PD-L1 expression and more T cells infiltration,but less PD-L1highCD11b+myeloid cells infiltration than MWA in HCC.Furthermore,CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models.Mech-anistically,anti-PD-L1 antibody facilitated infiltration of CD8+T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy.On the other hand,anti-PD-L1 antibody promoted the infil-tration of NK cells to eliminate PD-L1highCD11b+myeloid cells by antibody-dependent cell-mediated cytotoxicity(ADCC)effect after CRA therapy.Both aspects relieved the immunosuppressive microenvironment after CRA therapy.Notably,the wild-type PD-L1 Avelumab(Bavencio),compared to the mutant PD-L1 atezolizumab(Tecentriq),was better at inducing the ADCC effect to target PD-L1high-CD11b+myeloid cells.Collectively,our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell im-mune responses,which provided a strong rationale for combining CRA and PD-L1 blockade in the clin-ical treatment for HCC.
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