Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study

Cristina Maccalli, Diana Giannarelli, Filippo Capocefalo, Lorenzo Pilla, Ester Fonsatti, Anna Maria Di Giacomo, Giorgio Parmiani, Michele Maio

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11 Citations (Scopus)

Abstract

Clinical activity was observed in metastatic melanoma (MM) patients treated with ipilimumab (IPI) combined with fotemustine (FTM) in the phase II NIBIT-M1 study. Peripheral blood mononuclear cells (PBMCs) and serum were collected from MM patients at pre- and at weeks 12 and 24 post-treatment. A comprehensive phenotypic and functional immunomonitoring of circulating T cells, and the detection of soluble immunoregulatory molecules was carried out and correlated with clinical outcome. The frequency at baseline and along the treatment of circulating T central memory cells expressing activation/differentiation markers, such as CD3+CD4+CD45RO+BTLA+, CD3+CD4+4–1BB or Th17 lymphocytes correlated with the clinical outcome of MM patients. Moreover, either the absence or the presence of soluble NKG2D ligands (ULBP-1 or −2) at baseline in the serum of MM patients enabled to discriminate subjects with long-term survival (median overall survival, (OS) = 33.6 mo for ULBP-1 and −2) from poor survivors (OS = 9.8 or 6.6 mo, respectively). Conversely, no significant association between the levels of soluble MICA, MICB and ULBP-3 and the clinical outcome of patients was observed. An inverse correlation between circulating levels of these molecules at baseline and frequency of either CD3+CD4+CD45RO+BTLA+ or Th17 or CD3+CD4+4–1BB+ T cells occurred in patients with a favorable clinical outcome. The simultaneous monitoring of different immune parameters, though validation in a large cohort of patients is needed, allowed to identify an association between phenotypic and soluble markers representing a possible predictive immunological signature for the clinical activity of IPI plus FTM.

Original languageEnglish
JournalOncoImmunology
Volume5
Issue number2
DOIs
Publication statusPublished - 1 Feb 2016
Externally publishedYes

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Keywords

  • Cytotoxic T-lymphocyte Antigen-4 (CTLA-4)
  • Melanoma
  • NKG2D ligands
  • T cell subsets

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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