Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients

Cristina Maccalli, Diana Giannarelli, Carla Chiarucci, Ornella Cutaia, Gianluca Giacobini, Wouter R. Hendrickx, Giovanni Amato, Diego Annesi, Davide Bedognetti, Maresa Altomonte, Riccardo Danielli, Luana Calabrò, Anna Maria Di Giacomo, Francesco M. Marincola, Giorgio Parmiani, Michele Maio

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The introduction of immune checkpoint blockade into the clinical practice resulted in improvement of survival of a significant portion of melanoma patients. Consequently, predictive biomarkers of response are needed to optimize patient's stratification and the development of combination therapies. The aim of this study was to determine whether levels of soluble NKG2D ligands (MICA, MICB, ULBP1, 2 and 3; sNKG2DLs) in the serum of melanoma patients can serve as useful predictors of response to the treatment with immune checkpoint blockade. sNKG2DLs were measured by ELISA in baseline and post-treatment serum and these results were correlated with the clinical outcome of melanoma patients (N = 194). The same determinations were performed also in a cohort of patients (N = 65) treated with either chemotherapy, radiotherapy, or mutated BRAF inhibitors (BRAFi). Absence of soluble MICB and ULBP-1 in baseline serum correlated with improved survival (OS = 21.6 and 25.3 mo and p = 0.02 and 0.01, respectively) of patients treated with immunological therapies while detectable levels of these molecules were found in poor survivors (OS = 8.8 and 12.1 mo, respectively). Multivariate analysis showed that LDH (p <0.0001), sULBP-1 (p = 0.02), and sULBP-2 (p = 0.02) were independent predictors of clinical outcome for the cohort of melanoma patients treated with immune checkpoint blockade. Only LDH but not sNKG2DLs was significantly associated with the clinical outcome of patients treated with standard or BRAFi regimens. These findings highlight the relevance of sNKG2DLs in the serum of melanoma patients as biomarkers for patients' stratification and optimization of immune checkpoint inhibition regimens.

Original languageEnglish
Article numbere1323618
JournalOncoImmunology
Volume6
Issue number7
DOIs
Publication statusPublished - 3 Jul 2017

Fingerprint

Melanoma
Biomarkers
Ligands
Therapeutics
Serum
Survival
Survivors
Radiotherapy
Multivariate Analysis
Enzyme-Linked Immunosorbent Assay
Drug Therapy

Keywords

  • Cytotoxic T-lymphocyte antigen-4 (CTLA-4)
  • metastatic melanoma
  • NKG2D ligands
  • programmed cell death-1 (PD-1)
  • T cell responses

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients. / Maccalli, Cristina; Giannarelli, Diana; Chiarucci, Carla; Cutaia, Ornella; Giacobini, Gianluca; Hendrickx, Wouter R.; Amato, Giovanni; Annesi, Diego; Bedognetti, Davide; Altomonte, Maresa; Danielli, Riccardo; Calabrò, Luana; Di Giacomo, Anna Maria; Marincola, Francesco M.; Parmiani, Giorgio; Maio, Michele.

In: OncoImmunology, Vol. 6, No. 7, e1323618, 03.07.2017.

Research output: Contribution to journalArticle

Maccalli, C, Giannarelli, D, Chiarucci, C, Cutaia, O, Giacobini, G, Hendrickx, WR, Amato, G, Annesi, D, Bedognetti, D, Altomonte, M, Danielli, R, Calabrò, L, Di Giacomo, AM, Marincola, FM, Parmiani, G & Maio, M 2017, 'Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients', OncoImmunology, vol. 6, no. 7, e1323618. https://doi.org/10.1080/2162402X.2017.1323618
Maccalli, Cristina ; Giannarelli, Diana ; Chiarucci, Carla ; Cutaia, Ornella ; Giacobini, Gianluca ; Hendrickx, Wouter R. ; Amato, Giovanni ; Annesi, Diego ; Bedognetti, Davide ; Altomonte, Maresa ; Danielli, Riccardo ; Calabrò, Luana ; Di Giacomo, Anna Maria ; Marincola, Francesco M. ; Parmiani, Giorgio ; Maio, Michele. / Soluble NKG2D ligands are biomarkers associated with the clinical outcome to immune checkpoint blockade therapy of metastatic melanoma patients. In: OncoImmunology. 2017 ; Vol. 6, No. 7.
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AU - Cutaia, Ornella

AU - Giacobini, Gianluca

AU - Hendrickx, Wouter R.

AU - Amato, Giovanni

AU - Annesi, Diego

AU - Bedognetti, Davide

AU - Altomonte, Maresa

AU - Danielli, Riccardo

AU - Calabrò, Luana

AU - Di Giacomo, Anna Maria

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