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Article: CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer

TitleCXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer
Authors
Keywordscolorectal cancer
CXCL8-CXCR1/2
dendritic cell (DC)
immune profiling
therapeutics
Issue Date2021
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology
Citation
Frontiers in Immunology, 2021, v. 12, p. article no. 667177 How to Cite?
AbstractAccumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vitro results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.
Persistent Identifierhttp://hdl.handle.net/10722/300617
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 1.868
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, E-
dc.contributor.authorYang, X-
dc.contributor.authorDu, Y-
dc.contributor.authorWang, G-
dc.contributor.authorChan, DW-
dc.contributor.authorWu, D-
dc.contributor.authorXu, P-
dc.contributor.authorNi, P-
dc.contributor.authorXu, D-
dc.contributor.authorHu, Y-
dc.date.accessioned2021-06-18T14:54:33Z-
dc.date.available2021-06-18T14:54:33Z-
dc.date.issued2021-
dc.identifier.citationFrontiers in Immunology, 2021, v. 12, p. article no. 667177-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/300617-
dc.description.abstractAccumulating evidence suggests that tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serve as promising therapeutic targets. CXCL8 (IL-8) may also be a potential therapeutic target in cancer. CXCL8 is a potent chemotactic factor for neutrophils, myeloid-derived suppressor cells (MDSCs) and monocytes, which are considered immunosuppressive components in cancer-bearing hosts. Here, we identified the TME-related gene CXCL8 in a high-ImmuneScore population that contributed to better survival in colorectal cancer (CRC) patients from The Cancer Genome Atlas (TCGA) database. An integrated gene profile and functional analysis of TIC proportions revealed that the dendritic cell (DC) activation markers CD80, CD83, and CD86 were positively correlated with CXCL8 expression, suggesting that CXCL8 may be functional as antitumor immune response status in the TME. The gene signature was further validated in independent GSE14333 and GSE38832 cohorts from the Gene Expression Omnibus (GEO). To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vitro results suggested no significant growth or survival changes following treatment with an inhibitor of the CXCL8 receptor (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Furthermore, CXCL8 induced DC migration in transwell migration assays. Taken together, our data suggested that targeting the CXCL8-CXCR2 axis might impede DC activation or recruitment, and this axis could be considered a favorable factor rather than a target for critical antitumor effects on CRC.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectcolorectal cancer-
dc.subjectCXCL8-CXCR1/2-
dc.subjectdendritic cell (DC)-
dc.subjectimmune profiling-
dc.subjecttherapeutics-
dc.titleCXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer-
dc.typeArticle-
dc.identifier.emailChan, DW: dwchan@hku.hk-
dc.identifier.authorityChan, DW=rp00543-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2021.667177-
dc.identifier.pmid34025668-
dc.identifier.pmcidPMC8138166-
dc.identifier.scopuseid_2-s2.0-85106149652-
dc.identifier.hkuros322765-
dc.identifier.volume12-
dc.identifier.spagearticle no. 667177-
dc.identifier.epagearticle no. 667177-
dc.identifier.isiWOS:000652554200001-
dc.publisher.placeSwitzerland-

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