MCT1 gene silencing enhances the immune effect of dendritic cells on cervical cancer cells.

IF 2.1 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Clinical and Experimental Medicine Pub Date : 2024-07-01 DOI:10.17219/acem/171446

Xiaoxin Sui, Xiaowei Xi

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Abstract

Background: Dendritic cells (DCs) are a key class of immune cells that migrate to the draining lymph nodes and present processed antigenic peptides to lymphocytes after being activated by external stimuli, thereby establishing adaptive immunity. Moreover, DCs play an important role in tumor immunity.

Objectives: The aim of the study was to investigate whether MCT1 gene silencing in DCs affects their ability to mount an immune response against cervical cancer cells.

Material and methods: We silenced the expression of MCT1 in DCs from mouse bone marrow (BM) by infection with adenovirus. The surface antigen profile of DCs was analyzed by flow cytometry and cytokine secretion was evaluated using enzyme-linked immunosorbent assay (ELISA) following sodium lactate (sLA) exposure and lipopolysaccharide (LPS) stimulation. Then, various groups of DC-induced cytotoxic T lymphocytes (CTLs) were prepared and their cytotoxicity against U14 was tested.

Results: Without sLA exposure, silencing MCT1 did not affect the expression of CD1a, CD80, CD83, CD86, and major histocompatibility complex class II (MHCII) in DCs after LPS challenge. Similar results were found for interleukin (IL)-6, IL-12 p70 and tumor necrosis factor alpha (TNF-α). After sLA exposure, silencing MCT1 significantly decreased the expression of CD1a, CD80, CD83, CD86, and MHCII in DCs after the LPS challenge, as well as the secretion of IL-6, IL-12 p70 and TNF-α. In addition, sLA exposure significantly reduced the toxicity and inhibited the proliferation of DC-induced CTLs compared to U14 cells in vitro and in vivo. However, silencing MCT1 significantly attenuated the changes caused by sLA exposure. At the same time, in the absence of sLA, silencing MCT1 did not affect the toxicity nor inhibit the proliferation of DC-induced CTLs on U14 cells.

Conclusions: Lactate exposure reduces the immune effect of DCs on cervical cancer cells, but MCT1 gene silencing attenuates these alterations.

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MCT1基因沉默可增强树突状细胞对宫颈癌细胞的免疫效应。

背景：树突状细胞（DC）是一类重要的免疫细胞，它们迁移到引流淋巴结，在受到外界刺激激活后，将处理过的抗原肽呈现给淋巴细胞，从而建立适应性免疫。此外，DCs 在肿瘤免疫中也发挥着重要作用：研究目的：本研究旨在探讨 MCT1 基因在 DCs 中的沉默是否会影响其对宫颈癌细胞的免疫应答能力：材料和方法：我们用腺病毒感染小鼠骨髓（BM）中的DCs，沉默其MCT1基因的表达。在乳酸钠（sLA）暴露和脂多糖（LPS）刺激下，用流式细胞术分析了DC的表面抗原谱，并用酶联免疫吸附试验（ELISA）评估了细胞因子的分泌。然后，制备了不同组的 DC 诱导的细胞毒性 T 淋巴细胞（CTLs），并测试了它们对 U14 的细胞毒性：结果：在不暴露 sLA 的情况下，沉默 MCT1 不会影响 LPS 挑战后 DC 中 CD1a、CD80、CD83、CD86 和主要组织相容性复合体 II 类（MHCII）的表达。白细胞介素（IL）-6、IL-12 p70和肿瘤坏死因子α（TNF-α）的表达也有类似的结果。暴露于 sLA 后，沉默 MCT1 能显著降低 LPS 挑战后 DCs 中 CD1a、CD80、CD83、CD86 和 MHCII 的表达，以及 IL-6、IL-12 p70 和 TNF-α 的分泌。此外，与体外和体内的U14细胞相比，暴露于sLA能明显降低毒性并抑制DC诱导的CTL的增殖。然而，沉默 MCT1 能明显减轻 sLA 暴露引起的变化。同时，在没有sLA的情况下，沉默MCT1不会影响毒性，也不会抑制DC诱导的CTL对U14细胞的增殖：结论：乳酸暴露会降低DC对宫颈癌细胞的免疫效应，但沉默MCT1基因可减轻这些改变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

3.70

自引率

4.80%

发文量

153

审稿时长

6-12 weeks

期刊介绍： Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.