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Clinical implication of tumor-associated and immunological parameters in melanoma patients treated with ipilimumab.
- Source :
-
Oncoimmunology [Oncoimmunology] 2016 Nov 01; Vol. 5 (12), pp. e1249559. Date of Electronic Publication: 2016 Nov 01 (Print Publication: 2016). - Publication Year :
- 2016
-
Abstract
- Ipilimumab, the first immune-checkpoint inhibitor extending overall survival (OS) in metastatic melanoma patients, has a survival benefit only in a proportion of patients and the development of reliable predictive biomarkers is still an unmet need. To meet this request, we used a multivariate statistical approach to test whether myeloid-derived suppressor cells (MDSC) or other tumor-associated and immunological parameters may serve as predictive or prognostic biomarkers in melanoma patients receiving ipilimumab. By using a standardized approach to determine the circulating levels of four MDSC subsets, we observed a significant expansion of three MDSC subsets at baseline, as compared to controls and, upon treatment, that high levels of CD14 <superscript>+</superscript> /IL4Rα <superscript>+</superscript> MDSCs were an independent prognostic factor of reduced OS. On the contrary, longer OS was associated to low levels of the proinflammatory proteins IL-6 and CRP and tumor-associated factors S100B and LDH both at baseline and after treatment. Increasing number of total T cells and especially of PD-1 <superscript>+</superscript> /CD4 <superscript>+</superscript> T cells were associated with better prognosis, and upregulation of PD-1 <superscript>+</superscript> expression on CD4 <superscript>+</superscript> T cells upon treatment was associated with lower toxicity. As several parameters were associated to OS, we included these factors in a multivariate survival model, and we identified IL-6 and ECOG PS as independent biomarkers associated with improved OS, whereas high levels of LDH and CD14 <superscript>+</superscript> /IL4Rα <superscript>+</superscript> MDSCs were negative independent markers of reduced OS.
Details
- Language :
- English
- ISSN :
- 2162-4011
- Volume :
- 5
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Oncoimmunology
- Publication Type :
- Academic Journal
- Accession number :
- 28123888
- Full Text :
- https://doi.org/10.1080/2162402X.2016.1249559