Ageing-mediated autophagy in natural killer(NK) cells:impairment of the function and potential of NK cells-based cancer immunotherapy
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- 英文论文题名：Ageing-mediated autophagy in natural killer(NK) cells:impairment of the function and potential of NK cells-based cancer immunotherapy
- 论文作者：Zhang Hangjie ; Zhao Min ; Liu Jun
- 英文论文作者：Zhang Hangjie ; Zhao Min ; Liu Jun ; CAS Key Laboratory of Pathogenic Microbiology and Immunology ; Institute of Microbiology ; Chinese Academy of Sciences
- 年：2016
- 作者机构：CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences;
- 英文论文关键词：NK ; ageing ; autophagy
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R730.51
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：350k
- 原文格式：D
- 会议级别：全国
摘要
Background: Natural killer(NK) cells are a promising immunotherapeutic approach in defense against tumor. Because ageing provokes effects on the immune system, and NK cells are derived from patients of young and old individuals, the consequent immunotherapy potential and immunological mechanism of ageing-mediated need to be further studied. Experimental Design: NK cells isolated from young and elderly human blood were co-cultured with tumor cells K562 to evaluate cellular interactions. ELISA, and FACS analysis were used to evaluate NK cells activation. Q-PCR and Western blot assays of LC3 were used to evaluate the induction of autophagy. Inhibitors/shRNA or overexpression targeting LC3 were utilized to investigate the mechanism of autophagy-mediated NK cells activation.Results: Compared with NK cells derived from elder, NK cells in young group have more potential to induce K562 death and increased the secretion of INF-γ and granzyme B. Interestingly, autophagy levels in NK cells of young group were displayed more than elder. Inhibitors/shRNA targeting LC3 in NK cells of young group, significantly inhibited NK cells activation and decreased anti-tumor efficacy.Conclusions: In this study, we describe a novel mechanism of ageing-mediated autophagy in NK cells, which provides a significant rationale for NK cells-based cancer immunotherapy to improve efficacy, and potentially offers novel immune modulators to improve aged immunity.
Background: Natural killer(NK) cells are a promising immunotherapeutic approach in defense against tumor. Because ageing provokes effects on the immune system, and NK cells are derived from patients of young and old individuals, the consequent immunotherapy potential and immunological mechanism of ageing-mediated need to be further studied. Experimental Design: NK cells isolated from young and elderly human blood were co-cultured with tumor cells K562 to evaluate cellular interactions. ELISA, and FACS analysis were used to evaluate NK cells activation. Q-PCR and Western blot assays of LC3 were used to evaluate the induction of autophagy. Inhibitors/sh RNA or overexpression targeting LC3 were utilized to investigate the mechanism of autophagy-mediated NK cells activation.Results: Compared with NK cells derived from elder, NK cells in young group have more potential to induce K562 death and increased the secretion of INF-γ and granzyme B. Interestingly, autophagy levels in NK cells of young group were displayed more than elder. Inhibitors/sh RNA targeting LC3 in NK cells of young group, significantly inhibited NK cells activation and decreased anti-tumor efficacy.Conclusions: In this study, we describe a novel mechanism of ageing-mediated autophagy in NK cells, which provides a significant rationale for NK cells-based cancer immunotherapy to improve efficacy, and potentially offers novel immune modulators to improve aged immunity.
Background: Natural killer(NK) cells are a promising immunotherapeutic approach in defense against tumor. Because ageing provokes effects on the immune system, and NK cells are derived from patients of young and old individuals, the consequent immunotherapy potential and immunological mechanism of ageing-mediated need to be further studied. Experimental Design: NK cells isolated from young and elderly human blood were co-cultured with tumor cells K562 to evaluate cellular interactions. ELISA, and FACS analysis were used to evaluate NK cells activation. Q-PCR and Western blot assays of LC3 were used to evaluate the induction of autophagy. Inhibitors/sh RNA or overexpression targeting LC3 were utilized to investigate the mechanism of autophagy-mediated NK cells activation.Results: Compared with NK cells derived from elder, NK cells in young group have more potential to induce K562 death and increased the secretion of INF-γ and granzyme B. Interestingly, autophagy levels in NK cells of young group were displayed more than elder. Inhibitors/sh RNA targeting LC3 in NK cells of young group, significantly inhibited NK cells activation and decreased anti-tumor efficacy.Conclusions: In this study, we describe a novel mechanism of ageing-mediated autophagy in NK cells, which provides a significant rationale for NK cells-based cancer immunotherapy to improve efficacy, and potentially offers novel immune modulators to improve aged immunity.
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