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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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作者 Jizhou Tana [1] Ting Liu [2] Wenzhe Fan [3] Jialiang Wei [3] Bowen Zhu [3] Yafang Liu [4] Lingwei Liu [3] Xiaokai Zhang [3] Songling Chen [4] Haibiao Lin [2] Yuanqing Zhang [5] Jiaping Li [3] 学术成果认领
作者单位 Department of Interventional Oncology,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China;Department of Stomatology,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China [1] Department of Laboratory Medicine,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangdong Provincial Hospital of Traditional,Chinese Medicine,Guangzhou 510120,China;Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510006,China [2] Department of Interventional Oncology,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China [3] Department of Stomatology,the First Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China [4] School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China [5]
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发布时间 2023-04-21
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