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Author:

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

Indexed by:

Scopus SCIE PubMed

Abstract:

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.

Keyword:

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

Author Community:

  • [ 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

Reprint Author's Address:

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

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Source :

BIOMEDICINE & PHARMACOTHERAPY

ISSN: 0753-3322

Year: 2020

Volume: 121

7 . 5 0 0

JCR@2022

ESI Discipline: PHARMACOLOGY & TOXICOLOGY;

ESI HC Threshold:105

Cited Count:

WoS CC Cited Count: 10

SCOPUS Cited Count: 13

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 7

Online/Total:219/10662819
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