Anti-PD-L1 antibody enhances curative effect of cryoablation via antibody-dependent cell-mediated cytotoxicity mediating PD-L1highCD11b+ cells elimination in hepatocellular carcinoma.
10.1016/j.apsb.2022.08.006
- Author:
Jizhou TAN
1
;
Ting LIU
2
;
Wenzhe FAN
1
;
Jialiang WEI
1
;
Bowen ZHU
1
;
Yafang LIU
3
;
Lingwei LIU
1
;
Xiaokai ZHANG
1
;
Songling CHEN
3
;
Haibiao LIN
2
;
Yuanqing ZHANG
4
;
Jiaping LI
1
Author Information
1. Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
2. Department of Laboratory Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Traditional, Chinese Medicine, Guangzhou 510120, 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.
- Publication Type:Journal Article
- Keywords:
Antibody-dependent cell-mediated cytotoxicity;
CXCL9;
Cryoablation;
Hepatocellular carcinoma;
Immunosuppressive microenvironment;
Immunotherapy;
Microwave ablation;
NK cells
- From:
Acta Pharmaceutica Sinica B
2023;13(2):632-647
- CountryChina
- Language:English
-
Abstract:
Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular 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. Mechanistically, 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 infiltration 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-L1highCD11b+ 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 immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.
