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Assessment of interferon-γ in pleural fluid as a prognostic factor of survival in malignant pleural mesothelioma

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Abstract

Backgound

Literature reports suggest that the host immune system may control Malignant Pleural Mesothelioma (MPM) growth, although its activity is limited by regulatory mechanisms. In this retrospective study, we analyzed the levels of pro-inflammatory (IL-1, IL-6, TNF), immune-regulatory (IL-10) and Th1/CTL-related cytokines (IL-12p70, IFN-γ) in the pleural exudate and their relationship with overall survival (OS) in MPM.

Methods

Cytokines were quantified by multiplexed immunoassay. Concentrations were dichotomized with respect to the median value. Correlation between cytokine level and OS was assessed using univariate (Kaplan–Meier curves) and multivariate (Cox regression) analyses.

Results

Regarding outcome, tumor histology, therapies undergone and IFN-γ were independent prognostic factors of OS in a 72 MPM training cohort. Notably, high concentrations of IFN-γ halved death probability (HR of high vs low IFN-γ concentration = 0.491, 95%CI 0.3–0.8, p = 0.007). Also in patients with epithelioid histology and those receiving at least one line of therapy, high IFN-γ level was an independent factor predictive of OS (HR of high vs low IFN-γ concentration were 0.497, p = 0.007 and 0.324, p = 0.006, respectively). However, these data were not confirmed in a 77 MPM validation cohort, possibly due to the low IFN-γ levels encountered in this population, and the heterogeneous distribution of disease stages between the training and the validation cohorts. None of the other cytokines showed any effect on survival.

Conclusions

High level of IFN-γ in pleural effusion may be associated with better survival in MPM patients and potentially serve as a prognostic biomarker. Larger prospective studies are needed to ascertain this hypothesis.

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Acknowledgements

We thank Stefania Martini for excellent technical assistance and the Azienda Ospedaliera di Alessandria Biorepository “Alessandria Biobank” for providing the validation cohort

Funding

Funding

This work was supported by grants from the Italian Ministry of Health (GR-2013–02356568, Ricerca Corrente and 5 × 1000 Funds).

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Author notes

  1. Beatrice Dozin and Grazia Carbotti have contributed equally.

Authors and Affiliations

  1. Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Beatrice Dozin

  2. Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo Benzi 10, 16132, Genoa, Italy

    Grazia Carbotti, Silvano Ferrini & Marina Fabbi

  3. Histopathology and Cytopathology Division, Azienda Sanitaria Locale N. 5 , La Spezia, Italy

    Silvio Roncella, Paola Ferro & Paolo Dessanti

  4. Pneumology Division, Azienda Sanitaria Locale N. 5 , La Spezia, Italy

    Pier Aldo Canessa

Authors
  1. Beatrice Dozin
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  2. Grazia Carbotti
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  4. Paola Ferro
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  7. Silvano Ferrini
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  8. Marina Fabbi
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Contributions

Study concept and design, and study supervision: SF, MF, Recruitment of MPM patients: SR, PF, PD, PAC, Acquisition, analysis or interpretation of data: BD, GC, SF, MF, Manuscript drafting: BD, GC, SF, MF, Statistical analyses: BD, Critical revision of the manuscript for important intellectual content: SF, All authors read and approved the final manuscript.

Corresponding author

Correspondence to Marina Fabbi.

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Conflict of interest

The author declares there is no conflict of interest.

Ethical approval

The local Ethical Committee (Azienda Sanitaria Locale n.5 La Spezia) approved the study (P.R. 207REG2014). All procedures performed in the study were in accordance with the Declaration of HELSINKI.

Informed consent

All patients provided a signed informed consent before enrollment.

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Dozin, B., Carbotti, G., Roncella, S. et al. Assessment of interferon-γ in pleural fluid as a prognostic factor of survival in malignant pleural mesothelioma. Cancer Immunol Immunother 70, 3349–3355 (2021). https://doi.org/10.1007/s00262-021-02965-w

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  • DOI: https://doi.org/10.1007/s00262-021-02965-w

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