{"title":"MCT1 gene silencing enhances the immune effect of dendritic cells on cervical cancer cells.","authors":"Xiaoxin Sui, Xiaowei Xi","doi":"10.17219/acem/171446","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objectives: </strong>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.</p><p><strong>Material and methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>Lactate exposure reduces the immune effect of DCs on cervical cancer cells, but MCT1 gene silencing attenuates these alterations.</p>","PeriodicalId":7306,"journal":{"name":"Advances in Clinical and Experimental Medicine","volume":" ","pages":"739-749"},"PeriodicalIF":2.1000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Clinical and Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.17219/acem/171446","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
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.
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.
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