Clinical implication of tumor-associated and immunological parameters in melanoma patients treated with ipilimumab

Vera Damuzzo, Saniantha Solito, Laura Pinton, E. Carrozzo, S. Valpione, J. Pigozzo, R. Arboretti Giancristofaro, V. Chiarion-Sileni, S. Mandruzzato

Research output: Contribution to journalArticle

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+/IL4Rα+ 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+/CD4+ T cells were associated with better prognosis, and upregulation of PD-1+ expression on CD4+ 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+/IL4Rα+ MDSCs were negative independent markers of reduced OS.

Original languageEnglish
Article numbere1249559
JournalOncoImmunology
Volume5
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Keywords

  • Biomarkers
  • CTLA-4
  • ipilimumab
  • melanoma
  • myeloid-derived suppressor cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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