CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor

Silvio Roncella, Stefania Laurent, Vincenzo Fontana, Paola Ferro, Maria Cristiana Franceschini, Sandra Salvi, Serena Varesano, Simona Boccardo, Antonella Vigani, Anna Morabito, Pier Aldo Canessa, Ugo Giannoni, Ilan Rosenberg, Alessandro Valentino, Franco Fedeli, Domenico Franco Merlo, Marcello Ceppi, Salvatore Riggio, Massimo Romani, Daniele SaverinoAlessandro Poggi, Maria Pia Pistillo

Research output: Contribution to journalArticle

Abstract

CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18–0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalCancer Immunology, Immunotherapy
DOIs
Publication statusAccepted/In press - May 20 2016

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Mesothelioma
Body Fluids
Pleural Effusion
Serum
Survival
Protein Isoforms
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Malignant Mesothelioma
T-Lymphocytes
Mortality
Neoplasms

Keywords

  • CTLA-4
  • Mesothelioma
  • Overall survival
  • Pleural effusion
  • Prognostic factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

CTLA-4 in mesothelioma patients : tissue expression, body fluid levels and possible relevance as a prognostic factor. / Roncella, Silvio; Laurent, Stefania; Fontana, Vincenzo; Ferro, Paola; Franceschini, Maria Cristiana; Salvi, Sandra; Varesano, Serena; Boccardo, Simona; Vigani, Antonella; Morabito, Anna; Canessa, Pier Aldo; Giannoni, Ugo; Rosenberg, Ilan; Valentino, Alessandro; Fedeli, Franco; Merlo, Domenico Franco; Ceppi, Marcello; Riggio, Salvatore; Romani, Massimo; Saverino, Daniele; Poggi, Alessandro; Pistillo, Maria Pia.

In: Cancer Immunology, Immunotherapy, 20.05.2016, p. 1-9.

Research output: Contribution to journalArticle

Roncella, S, Laurent, S, Fontana, V, Ferro, P, Franceschini, MC, Salvi, S, Varesano, S, Boccardo, S, Vigani, A, Morabito, A, Canessa, PA, Giannoni, U, Rosenberg, I, Valentino, A, Fedeli, F, Merlo, DF, Ceppi, M, Riggio, S, Romani, M, Saverino, D, Poggi, A & Pistillo, MP 2016, 'CTLA-4 in mesothelioma patients: tissue expression, body fluid levels and possible relevance as a prognostic factor', Cancer Immunology, Immunotherapy, pp. 1-9. https://doi.org/10.1007/s00262-016-1844-3
Roncella, Silvio ; Laurent, Stefania ; Fontana, Vincenzo ; Ferro, Paola ; Franceschini, Maria Cristiana ; Salvi, Sandra ; Varesano, Serena ; Boccardo, Simona ; Vigani, Antonella ; Morabito, Anna ; Canessa, Pier Aldo ; Giannoni, Ugo ; Rosenberg, Ilan ; Valentino, Alessandro ; Fedeli, Franco ; Merlo, Domenico Franco ; Ceppi, Marcello ; Riggio, Salvatore ; Romani, Massimo ; Saverino, Daniele ; Poggi, Alessandro ; Pistillo, Maria Pia. / CTLA-4 in mesothelioma patients : tissue expression, body fluid levels and possible relevance as a prognostic factor. In: Cancer Immunology, Immunotherapy. 2016 ; pp. 1-9.
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T2 - tissue expression, body fluid levels and possible relevance as a prognostic factor

AU - Roncella, Silvio

AU - Laurent, Stefania

AU - Fontana, Vincenzo

AU - Ferro, Paola

AU - Franceschini, Maria Cristiana

AU - Salvi, Sandra

AU - Varesano, Serena

AU - Boccardo, Simona

AU - Vigani, Antonella

AU - Morabito, Anna

AU - Canessa, Pier Aldo

AU - Giannoni, Ugo

AU - Rosenberg, Ilan

AU - Valentino, Alessandro

AU - Fedeli, Franco

AU - Merlo, Domenico Franco

AU - Ceppi, Marcello

AU - Riggio, Salvatore

AU - Romani, Massimo

AU - Saverino, Daniele

AU - Poggi, Alessandro

AU - Pistillo, Maria Pia

PY - 2016/5/20

Y1 - 2016/5/20

N2 - CTLA-4 function as a negative regulator of T cell-mediated immune response is well established, whereas much less is known about the immunoregulatory role of its soluble isoform (sCTLA-4). No data are available on CTLA-4 expression and prognostic impact in malignant pleural mesothelioma (MPM). We investigated, by immunohistochemistry, CTLA-4 expression in tumor tissues and, by ELISA, sCTLA-4 levels in sera and matched pleural effusions from 45 MPM patients. Prognostic effect of CTLA-4 expression on overall survival (OS) was assessed through Cox regression and prognostic significance expressed as death rate ratio (HR). We found that 56.0 % of MPM tissues expressed CTLA-4 with variable intensity and percentage of positive cells estimated by the immunoreactive score. sCTLA-4 levels were significantly higher in sera (S-sCTLA-4) than in pleural effusions (PE-sCTLA-4) (geometric mean ratio = 2.70, P value = 0.020). CTLA-4 expression at the tissue level was higher in the epithelioid histological subtype than in the sarcomatoid, whereas at the serum level, it was higher in the sarcomatoid subtype. A homogeneous favorable prognostic effect was found for CTLA-4 overexpression in tissue, serum and pleural effusion. Interestingly, only the PE-sCTLA-4 was found to be a statistically significant positive prognostic factor (HR = 0.37, 95 % CI = 0.18–0.77, P value = 0.007). Indeed, PE-sCTLA-4 correlated with CTLA-4 expression in tissues, whereas this latter expression showed a weak association with OS. To confirm our findings, further experimental evidences obtained from a larger cohort of MPM patients are required. However, our results would indicate a positive correlation of PE-sCTLA-4 levels and OS in MPM patients.

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KW - Overall survival

KW - Pleural effusion

KW - Prognostic factor

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