Role of Immune Response, Inflammation, and Tumor Immune Response–Related Cytokines/Chemokines in Melanoma Progression

Shenying Fang, Tao Xu, Momiao Xiong, Xinke Zhou, Yuling Wang, Lauren E. Haydu, Merrick I. Ross, Jeffrey E. Gershenwald, Victor G. Prieto, Janice N. Cormier, Jennifer Wargo, Dawen Sui, Qingyi Wei, Christopher I. Amos, Jeffrey E. Lee

Research output: Contribution to journalArticle

Abstract

To investigate the role of tumor cytokines/chemokines in melanoma immune response, we estimated the proportions of immune cell subsets in melanoma tumors from The Cancer Genome Atlas, followed by evaluation of the association between cytokine/chemokine expression and these subsets. We then investigated the association of immune cell subsets, chemokines, and cytokines with patient survival. Finally, we evaluated the immune cell tumor-infiltrating lymphocyte (TIL) score for correlation with melanoma patient outcome in a separate cohort. There was good agreement between RNA sequencing estimation of T-cell subset and pathologist-determined TIL score. Expression levels of cytokines IL-12A, IFNG, and IL-10, and chemokines CXCL9 and CXCL10 were positively correlated with PDCD1, CTLA-4, and CD8+ T-cell subset, but negatively correlated with tumor purity (Bonferroni-corrected P < 0.05). In multivariable analysis, higher expression levels of cytokines IFN-γ and TGFB1, but not chemokines, were associated with improved overall survival. A higher expression level of CD8+ T-cell subset was also associated with improved overall survival (hazard ratio [HR] = 0.06, 95% confidence interval [CI] = 0.01–0.35, P = 0.002). Finally, multivariable analysis showed that patients with a brisk TIL score had improved melanoma-specific survival than those with a nonbrisk score (HR = 0.51, 95% CI = 0.27–0.98, P = 0.0423). These results suggest that the expression of specific tumor cytokines represents important biomarkers of melanoma immune response.

Original languageEnglish (US)
Pages (from-to)2352-2358.e3
JournalJournal of Investigative Dermatology
Volume139
Issue number11
DOIs
StatePublished - Nov 2019

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Chemokines
Tumors
Melanoma
Cytokines
Inflammation
Tumor-Infiltrating Lymphocytes
T-Lymphocyte Subsets
T-cells
Lymphocytes
Neoplasms
Survival
Chemokine CXCL9
Hazards
Chemokine CXCL10
Confidence Intervals
RNA Sequence Analysis
Association reactions
Atlases
Interleukin-10
Biomarkers

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Role of Immune Response, Inflammation, and Tumor Immune Response–Related Cytokines/Chemokines in Melanoma Progression. / Fang, Shenying; Xu, Tao; Xiong, Momiao; Zhou, Xinke; Wang, Yuling; Haydu, Lauren E.; Ross, Merrick I.; Gershenwald, Jeffrey E.; Prieto, Victor G.; Cormier, Janice N.; Wargo, Jennifer; Sui, Dawen; Wei, Qingyi; Amos, Christopher I.; Lee, Jeffrey E.

In: Journal of Investigative Dermatology, Vol. 139, No. 11, 11.2019, p. 2352-2358.e3.

Research output: Contribution to journalArticle

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abstract = "To investigate the role of tumor cytokines/chemokines in melanoma immune response, we estimated the proportions of immune cell subsets in melanoma tumors from The Cancer Genome Atlas, followed by evaluation of the association between cytokine/chemokine expression and these subsets. We then investigated the association of immune cell subsets, chemokines, and cytokines with patient survival. Finally, we evaluated the immune cell tumor-infiltrating lymphocyte (TIL) score for correlation with melanoma patient outcome in a separate cohort. There was good agreement between RNA sequencing estimation of T-cell subset and pathologist-determined TIL score. Expression levels of cytokines IL-12A, IFNG, and IL-10, and chemokines CXCL9 and CXCL10 were positively correlated with PDCD1, CTLA-4, and CD8+ T-cell subset, but negatively correlated with tumor purity (Bonferroni-corrected P < 0.05). In multivariable analysis, higher expression levels of cytokines IFN-γ and TGFB1, but not chemokines, were associated with improved overall survival. A higher expression level of CD8+ T-cell subset was also associated with improved overall survival (hazard ratio [HR] = 0.06, 95{\%} confidence interval [CI] = 0.01–0.35, P = 0.002). Finally, multivariable analysis showed that patients with a brisk TIL score had improved melanoma-specific survival than those with a nonbrisk score (HR = 0.51, 95{\%} CI = 0.27–0.98, P = 0.0423). These results suggest that the expression of specific tumor cytokines represents important biomarkers of melanoma immune response.",
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AU - Xu, Tao

AU - Xiong, Momiao

AU - Zhou, Xinke

AU - Wang, Yuling

AU - Haydu, Lauren E.

AU - Ross, Merrick I.

AU - Gershenwald, Jeffrey E.

AU - Prieto, Victor G.

AU - Cormier, Janice N.

AU - Wargo, Jennifer

AU - Sui, Dawen

AU - Wei, Qingyi

AU - Amos, Christopher I.

AU - Lee, Jeffrey E.

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