Unknown

Dataset Information

0

Preferential Expression of Programmed Death Ligand 1 Protein in Tumor-Associated Macrophages and Its Potential Role in Immunotherapy for Hepatocellular Carcinoma.


ABSTRACT: 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.

SUBMITTER: Park DJ 

PROVIDER: S-EPMC8124544 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Preferential Expression of Programmed Death Ligand 1 Protein in Tumor-Associated Macrophages and Its Potential Role in Immunotherapy for Hepatocellular Carcinoma.

Park Dong-Jun DJ   Sung Pil-Soo PS   Lee Gil-Won GW   Cho Sungwoo S   Kim Sung-Min SM   Kang Byung-Yoon BY   Hur Wonhee W   Yang Hyun H   Lee Soon-Kyu SK   Lee Sung-Hak SH   Jung Eun-Sun ES   Seo Chang-Ho CH   Ahn Joseph J   Choi Ho-Joong HJ   You Young-Kyoung YK   Jang Jeong-Won JW   Bae Si-Hyun SH   Choi Jong-Young JY   Yoon Seung-Kew SK  

International journal of molecular sciences 20210429 9


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<sup>+</sup> macrophages in the tumor microenvironment of HCC, suggestive of its expression in TAMs r  ...[more]

Similar Datasets

| S-EPMC8316870 | biostudies-literature
| S-EPMC6926111 | biostudies-literature
| S-EPMC4406806 | biostudies-literature
| S-EPMC8554719 | biostudies-literature
| S-EPMC8034578 | biostudies-literature
| S-EPMC9931715 | biostudies-literature
| S-EPMC8222171 | biostudies-literature
| S-EPMC8518358 | biostudies-literature
| S-EPMC2705348 | biostudies-literature