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作者:

Ge, Yuyang (Ge, Yuyang.) | Zhou, Zhixiang (Zhou, Zhixiang.) (学者:周志祥) | Wang, Xiaoli (Wang, Xiaoli.) | Zhou, Yubai (Zhou, Yubai.) | Liu, Wei (Liu, Wei.) | Teng, Zhiping (Teng, Zhiping.) | Zeng, Yi (Zeng, Yi.)

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摘要:

Immunotherapeutic strategies based on Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2) antigen-specific cytotoxic T lymphocytes (CTLs) have been proven to boost LMP2-specific CTL responses in patients with nasopharyngeal carcinoma (NPC). Such strategies can produce clinical benefits in some patients with NPC. Currently, the major challenge limiting the use of immunotherapy for NPC is its low clinical response rate. The efficacy of immunotherapy based on EBV-LMP2 specific CTLs depends mainly on their cytotoxic activity, but no studies have been conducted to elucidate this activity. In this study, laser confocal scanning microscopy (LCSM) and real-time cell analysis (RTCA) were used to evaluate the killing function and its underlying mechanism of LMP2-specific CTLs. LCSM showed that LMP2-specific CTLs recognize and kill target cells expressing viral escape protein LMP2, and that the killing rate is related to the number of CTLs adhering to the target cells. LMP2-specific CTL-mediated cytotoxicity is rate limited by the time required for effective contact and recognition between CTLs and target cells. RTCA showed that the protective effect of LMP2-specific CTLs required an appropriate effector-to-target ratio, and that LMP2-specific CTLs could not eradicate residual target cells at a low effector-to-target ratio. Moreover, our results revealed that LMP2-specific CTL responses involve two independent but complementary mechanisms: the perforin/granzyme and Fas/FasL pathways. Therefore, we have elucidated, for the first time, the selective cytotoxicity and mechanism by which LMP2-specific CTLs induced by the rAd-LMP2 vaccine kill target cells and have explored the killing mode and several key parameters of killing mediated by LMP2-specific CTLs. Our study will contribute to the knowledge of vaccines targeting EBV-LMP2 and to the improvement of immunotherapeutic strategies.

关键词:

Cytotoxic T lymphocytes Epstein-Barr virus Immunotherapy Latent membrane protein 2 Nasopharyngeal carcinoma Vaccine

作者机构:

  • [ 1 ] [Ge, Yuyang]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 2 ] [Zhou, Zhixiang]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 3 ] [Wang, Xiaoli]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 4 ] [Zhou, Yubai]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 5 ] [Liu, Wei]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 6 ] [Teng, Zhiping]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 7 ] [Zeng, Yi]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China
  • [ 8 ] [Zeng, Yi]Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China

通讯作者信息:

  • [Zeng, Yi]Beijing Univ Technol, Coll Life Sci & Bioengn, Beijing 100124, Peoples R China

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来源 :

BIOMEDICINE & PHARMACOTHERAPY

ISSN: 0753-3322

年份: 2020

卷: 121

7 . 5 0 0

JCR@2022

ESI学科: PHARMACOLOGY & TOXICOLOGY;

ESI高被引阀值:25

JCR分区:1

被引次数:

WoS核心集被引频次: 10

SCOPUS被引频次: 13

ESI高被引论文在榜: 0 展开所有

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