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pmid:34025668

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

Enhao Li · Xiaobao Yang · Yuzhang Du · Guanzheng Wang · David W Chan · Di Wu · Peiqing Xu · Peihua Ni · Dakang Xu · Yiqun Hu

Frontiers in immunology · 2021 doi:10.3389/fimmu.2021.667177

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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title
CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer.
doi
10.3389/fimmu.2021.667177
pmid
34025668
authors array · 10 items
[0]
Enhao Li
[1]
Xiaobao Yang
[2]
Yuzhang Du
[3]
Guanzheng Wang
[4]
David W Chan
[5]
Di Wu
[6]
Peiqing Xu
[7]
Peihua Ni
[8]
Dakang Xu
[9]
Yiqun Hu
journal
Frontiers in immunology
year
2021
abstract
Accumulating 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.
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or (CXCR1/2) such as reparixin or danirixin. In vivo treatment with danirixin (antagonists of CXC
[1]
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Survival analyses were performed to assess the prognostic value of the indexes used in the study. The Kaplan-Meier (K-M) analysis was used to plot survival curves via the log-rank test.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34025668", "kind": "science-record", "revision": 7, "content_hash": "sha256:87a5b944497cdca65de243a37dfaddbe406b92ea9a1e79e2493051aea172eb3e", "created_at": "2026-11-01T15:41:36Z", "updated_at": "2026-11-01T22:46:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer.", "doi": "10.3389/fimmu.2021.667177", "pmid": "34025668", "authors": ["Enhao Li", "Xiaobao Yang", "Yuzhang Du", "Guanzheng Wang", "David W Chan", "Di Wu", "Peiqing Xu", "Peihua Ni", "Dakang Xu", "Yiqun Hu"], "journal": "Frontiers in immunology", "year": 2021, "abstract": "Accumulating 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.", "claims": [{"id": "claim-method", "statement": "Survival analyses were performed to assess the prognostic value of the indexes used in the study. The Kaplan-Meier (K-M) analysis was used to plot survival curves via the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34025668", "locator": "sections[17] \"Statistical and Survival Analyses\" paragraph 2", "quote": "Survival analyses were performed to assess the prognostic value of the indexes used in the study. The Kaplan-Meier (K-M) analysis was used to plot survival curves via the log-rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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