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 language | English (US) |
|---|---|
| Pages (from-to) | 2352-2358.e3 |
| Journal | Journal of Investigative Dermatology |
| Volume | 139 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2019 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Role of Immune Response, Inflammation, and Tumor Immune Response–Related Cytokines/Chemokines in Melanoma Progression
AU - Fang, Shenying
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.
PY - 2019/11
Y1 - 2019/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068891402&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068891402&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2019.03.1158
DO - 10.1016/j.jid.2019.03.1158
M3 - Article
C2 - 31176707
AN - SCOPUS:85068891402
VL - 139
SP - 2352-2358.e3
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 11
ER -