Nicotine exhausts CD8 + T cells against tumor cells through increasing miR-629-5p to repress IL2RB-mediated granzyme B e
- PDF / 4,668,235 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 14 Downloads / 191 Views
ORIGINAL ARTICLE
Nicotine exhausts CD8+ T cells against tumor cells through increasing miR‑629‑5p to repress IL2RB‑mediated granzyme B expression Chun‑Chia Cheng1 · Hsin‑Chi Lin6 · Ya‑Wen Chiang2,3 · Jungshan Chang5 · Zong‑Lin Sie1 · Bi‑Ling Yang6 · Ken‑Hong Lim2,3,4 · Cheng‑Liang Peng7 · Ai‑Sheng Ho6 · Yi‑Fang Chang2,3,4 Received: 28 April 2020 / Accepted: 15 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The mechanism exhausting C D8+ T cells is not completely clear against tumors. Literature has demonstrated that cigarette smoking disables the immunological activity, so we propose nicotine is able to exhaust CD8+ T cells. The CD8+ T cells from healthy volunteers with and without cigarette smoking and the capacity of CD8+ T cells against tumor cells were investigated. RNAseq was used to investigate the gene profiling expression in C D8+ T cells. Meanwhile, small RNAseq was + also used to search novel microRNAs involved in the exhaustion of CD8 T cells. The effect of nicotine exhausting CD8+ T cells was investigated in vitro and in the humanized tumor xenografts in vivo. We found that C D8+ T cells were able to reduce cell viability in lung cancer HCC827 and A549 cells, that secreted granzyme B, but C D8+ T cells from the healthy cigarette smokers lost anti-HCC827 effect. Moreover, nicotine suppressed the anti-HCC827 effect of CD8+ T cells. RNAseq revealed lower levels of IL2RB and GZMB in the exhausted C D8+ T cells. We identified that miR-629-5p was increased by nicotine, that targeted IL2RB. Transfection of miR-629-5p mimic reduced IL2RB and GZMB levels. We further validated that nicotine reduced granzyme B levels using a nuclear imaging technique, and demonstrated that nicotine exhausted peripheral blood mononuclear cells against HCC827 growth in the humanized tumor xenografts. This study demonstrated that nicotine exhausted CD8+ T cells against HCC827 cells through increasing miR-629-5p to suppress IL2RB. Keywords CD8+ T cells · Granzyme B · IL2RB · Nicotine
Introduction Cancer is a leading cause of death worldwide. Lung cancer that has higher prevalence and mortality is derived from contact with carcinogens [1]. There are several carcinogens that are directly responsible for promoting lung cancer, including tobacco smoking [2]. In exposure to carcinogens, free radicals are produced to damage lung cells and lead to lung cancers consequently. Meanwhile, tobacco smoking has also been demonstrated to suppress the immunological activity [3, 4], including adaptive immune T helper cells (Th1/Th2/ Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00262-020-02770-x) contains supplementary material, which is available to authorized users. * Ai‑Sheng Ho [email protected] * Yi‑Fang Chang [email protected] Extended author information available on the last page of the article
Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes, and innate dendritic cells (DCs), macrophages
Data Loading...
