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Preferential Expression of Programmed Death Ligand 1 Protein in Tumor-Associated Macrophages and Its Potential Role in Immunotherapy for Hepatocellular Carcinoma.
Park, Dong-Jun; Sung, Pil-Soo; Lee, Gil-Won; Cho, Sungwoo; Kim, Sung-Min; Kang, Byung-Yoon; Hur, Wonhee; Yang, Hyun; Lee, Soon-Kyu; Lee, Sung-Hak; Jung, Eun-Sun; Seo, Chang-Ho; Ahn, Joseph; Choi, Ho-Joong; You, Young-Kyoung; Jang, Jeong-Won; Bae, Si-Hyun; Choi, Jong-Young; Yoon, Seung-Kew.
Afiliação
  • Park DJ; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Sung PS; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Lee GW; Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
  • Cho S; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Kim SM; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Kang BY; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Hur W; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Yang H; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Lee SK; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Lee SH; Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul 03383, Korea.
  • Jung ES; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Seo CH; Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
  • Ahn J; Department of Clinical Pathology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
  • Choi HJ; Department of Hospital Pathology, College of Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul 03383, Korea.
  • You YK; Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
  • Jang JW; Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
  • Bae SH; Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
  • Choi JY; Department of Surgery, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea.
  • Yoon SK; The Catholic University Liver Research Center, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Int J Mol Sci ; 22(9)2021 Apr 29.
Article em En | MEDLINE | ID: mdl-33946835
A predictive biomarker of immune checkpoint inhibitor (ICI)-based treatments in hepatocellular carcinoma (HCC) has not been clearly demonstrated. In this study, we focused on the infiltration and programmed death ligand 1 (PD-L1) expression of tumor-associated macrophages (TAMs) in the tumor microenvironment of HCC. Immunohistochemistry demonstrated that PD-L1 was preferentially expressed on CD68+ macrophages in the tumor microenvironment of HCC, suggestive of its expression in TAMs rather than in T cells or tumor cells (P < 0.05). A co-culture experiment using activated T cells and M2 macrophages confirmed a significant increase in T cell functionality after the pretreatment of M2 macrophages with anti-PD-L1. Syngeneic mouse model experiments demonstrated that TAMs expressed PD-L1 and tumors treated with anti-PD-L1 showed smaller diameters than those treated with IgG. In these mice, anti-PD-L1 treatment increased activation markers in intratumoral CD8+ T cells and reduced the size of the TAM population. Regarding nivolumab-treated patients, three of eight patients responded to the anti-PD-1 treatment. The percentage of Ki-67-positive CD4+ and CD8+ T cells was higher in responders than non-responders after nivolumab. Overall, PD-L1 expression on TAMs may be targeted by immune-based HCC treatment, and ICI treatment results in the reinvigoration of exhausted CD8+ T cells in HCC.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Terapia de Alvo Molecular / Microambiente Tumoral / Antígeno B7-H1 / Antineoplásicos Imunológicos / Nivolumabe / Inibidores de Checkpoint Imunológico / Macrófagos Associados a Tumor / Imunoterapia / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Terapia de Alvo Molecular / Microambiente Tumoral / Antígeno B7-H1 / Antineoplásicos Imunológicos / Nivolumabe / Inibidores de Checkpoint Imunológico / Macrófagos Associados a Tumor / Imunoterapia / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article