PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma

CD3+CD56+ NKT-like cells play pivotal roles in the anti-tumor immune defense response. However, little is known regarding circulating NKT-like cells in patients with primary hepatocellular carcinoma (HCC). In the present study, we demonstrate that circulating NKT-like cells in HCC patients are funct...

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Autores principales:	Longxiang Tao, Shanshan Wang, Guijie Kang, Shanyue Jiang, Wenwei Yin, Lu Zong, Jing Li, Xuefu Wang
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	hepatocellular carcinoma nkt-like cells pd-1 immune exhaustion immunotherapy Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3becbfdb8c66467ea0c7941085bbb702
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spelling	oai:doaj.org-article:3becbfdb8c66467ea0c7941085bbb7022021-11-11T14:23:43ZPD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma2162-402X10.1080/2162402X.2021.2002068https://doaj.org/article/3becbfdb8c66467ea0c7941085bbb7022021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/2162402X.2021.2002068https://doaj.org/toc/2162-402XCD3+CD56+ NKT-like cells play pivotal roles in the anti-tumor immune defense response. However, little is known regarding circulating NKT-like cells in patients with primary hepatocellular carcinoma (HCC). In the present study, we demonstrate that circulating NKT-like cells in HCC patients are functionally impaired and anti-PD-1 blockade improves their anti-tumor potency. Circulating NKT cells were mainly comprised of CD8+ T cells. The frequencies and absolute counts of circulating NKT-like cells were comparable between HCC patents compared to healthy donors. NKT-like cells in HCC patients were impaired in their production of TNF-α and IFN-γ as well as cytotoxicity. The level of activating receptor NKG2D was significantly decreased on NKT-like cells in HCC patients. In contrast, the expression of inhibitory receptors PD-1, Tim-3, and CTLA-4 were markedly increased on NKT-like cells in HCC patients. Meanwhile, the expression of PD-L1 was also upregulated on NKT-like cells in HCC patients. In detail, PD-1+ NKT-like cells expressed lower levels of NKG2D, higher levels of Tim-3, and CTLA-4, and less IFN-γ when compared with PD-1− NKT-like cells. Importantly, PD-1 blocked with anti-PD-1 antibody effectively improved the effector function of NKT-like cells from HCC patients or healthy donors. Our findings unveil the functional characterization of NKT-like cells in HCC patients and provide the potential targets to improve their function, which might benefit the optimization of HCC immunotherapy.Longxiang TaoShanshan WangGuijie KangShanyue JiangWenwei YinLu ZongJing LiXuefu WangTaylor & Francis Grouparticlehepatocellular carcinomankt-like cellspd-1immune exhaustionimmunotherapyImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncoImmunology, Vol 10, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hepatocellular carcinoma nkt-like cells pd-1 immune exhaustion immunotherapy Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hepatocellular carcinoma nkt-like cells pd-1 immune exhaustion immunotherapy Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Longxiang Tao Shanshan Wang Guijie Kang Shanyue Jiang Wenwei Yin Lu Zong Jing Li Xuefu Wang PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma
description	CD3+CD56+ NKT-like cells play pivotal roles in the anti-tumor immune defense response. However, little is known regarding circulating NKT-like cells in patients with primary hepatocellular carcinoma (HCC). In the present study, we demonstrate that circulating NKT-like cells in HCC patients are functionally impaired and anti-PD-1 blockade improves their anti-tumor potency. Circulating NKT cells were mainly comprised of CD8+ T cells. The frequencies and absolute counts of circulating NKT-like cells were comparable between HCC patents compared to healthy donors. NKT-like cells in HCC patients were impaired in their production of TNF-α and IFN-γ as well as cytotoxicity. The level of activating receptor NKG2D was significantly decreased on NKT-like cells in HCC patients. In contrast, the expression of inhibitory receptors PD-1, Tim-3, and CTLA-4 were markedly increased on NKT-like cells in HCC patients. Meanwhile, the expression of PD-L1 was also upregulated on NKT-like cells in HCC patients. In detail, PD-1+ NKT-like cells expressed lower levels of NKG2D, higher levels of Tim-3, and CTLA-4, and less IFN-γ when compared with PD-1− NKT-like cells. Importantly, PD-1 blocked with anti-PD-1 antibody effectively improved the effector function of NKT-like cells from HCC patients or healthy donors. Our findings unveil the functional characterization of NKT-like cells in HCC patients and provide the potential targets to improve their function, which might benefit the optimization of HCC immunotherapy.
format	article
author	Longxiang Tao Shanshan Wang Guijie Kang Shanyue Jiang Wenwei Yin Lu Zong Jing Li Xuefu Wang
author_facet	Longxiang Tao Shanshan Wang Guijie Kang Shanyue Jiang Wenwei Yin Lu Zong Jing Li Xuefu Wang
author_sort	Longxiang Tao
title	PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma
title_short	PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma
title_full	PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma
title_fullStr	PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma
title_full_unstemmed	PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma
title_sort	pd-1 blockade improves the anti-tumor potency of exhausted cd3+cd56+ nkt-like cells in patients with primary hepatocellular carcinoma
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/3becbfdb8c66467ea0c7941085bbb702
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PD-1 blockade improves the anti-tumor potency of exhausted CD3+CD56+ NKT-like cells in patients with primary hepatocellular carcinoma

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