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Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell- mediated cytotoxicity mediating PD-L1highCD11bD cells elimination in hepatocellular carcinoma

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收录情况: ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C ◇ 卓越:领军期刊

机构: [1]Sun Yat sen Univ, Affiliated Hosp 1, Dept Intervent Oncol, Guangzhou 510080, Peoples R China [2]Sun Yat sen Univ, Affiliated Hosp 1, Dept Stomatol, Guangzhou 510080, Peoples R China [3]Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangdong Prov Hosp Tradit, Dept Lab Med, Guangzhou 510120, Peoples R China [4]Guangzhou Univ Chinese Med, Clin Med Coll 2, Guangzhou 510006, Peoples R China [5]Sun Yat sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Peoples R China
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关键词: Immunosuppressive microenvironment Hepatocellular carcinoma Immunotherapy Cryoablation Microwave ablation CXCL9 NK cells Antibody-dependent cell-mediated cytotoxicity

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. 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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大类 | 1 区 化学
小类 | 1 区 药学
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大类 | 1 区 医学
小类 | 1 区 药学
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Q1 PHARMACOLOGY & PHARMACY
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Q1 PHARMACOLOGY & PHARMACY

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第一作者机构: [1]Sun Yat sen Univ, Affiliated Hosp 1, Dept Intervent Oncol, Guangzhou 510080, Peoples R China [2]Sun Yat sen Univ, Affiliated Hosp 1, Dept Stomatol, Guangzhou 510080, Peoples R China
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