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

Our plain-English summary of Assessment of interferon-γ in pleural fluid as a prognostic factor of survival in malignant pleural mesothelioma, by B. Dozin, G. Carbotti, S. Roncella, et al (Cancer Immunology, Immunotherapy, 2021).

The study

• Authors: B. Dozin, G. Carbotti, S. Roncella, P. Ferro, P. Dessanti, P.A. Canessa, S. Ferrini, M. Fabbi
• Journal: Cancer Immunology, Immunotherapy
• Published: 2021;70(11):3349-3355
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

In plain English

This retrospective study from Italy measured six cytokines (immune signalling proteins: IL-1, IL-6, TNF, IL-10, IL-12p70 and interferon-gamma, or IFN-γ) in pleural fluid from people with malignant pleural mesothelioma. It then looked at whether the levels were linked to survival. The main (training) group was 72 patients recruited in La Spezia between June 2008 and May 2013. Levels were split at the median, which for IFN-γ was 13.8 pg/ml. Only IFN-γ was linked to survival. After adjusting for other factors, patients with higher IFN-γ had a hazard ratio for death of 0.49 (95% CI 0.3 to 0.8) compared with those with lower levels. Tumor type and receiving therapy were also independent factors. Reported asbestos exposure was not significantly associated with survival in this group (hazard ratio 1.41, 95% CI 0.8 to 2.4, exposed versus unexposed). In a second group of 77 patients' fluids from another Italian area, IFN-γ showed no link with survival. However, levels in that group were extremely low or undetectable, and its stage mix differed. The authors concluded that IFN-γ should be studied further as a possible prognostic marker in larger prospective studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of cytokine levels in stored pleural fluid and their relation to overall survival, with a training cohort and a separate validation cohort
• Who was studied: Training cohort: 72 malignant pleural mesothelioma patients from the Division of Pneumology, La Spezia, Italy, recruited June 2008 to May 2013. Validation cohort: 77 MPM pleural fluids from the Alessandria Biobank, a different Italian area that also has high MPM incidence.
• Exposure: The factor studied was pleural fluid cytokine levels, not asbestos dose. Asbestos exposure was recorded only as yes or no: 44 of 72 patients (61.1%) yes, 26 (36.1%) no, 2 unknown. No fiber types were reported.
• Main results:
  • Training cohort: all but 2 patients had died by the end of observation. Overall median survival was 13.5 months (95% CI 11.3 to 15.6).
  • Training cohort, univariate analysis: 30-month survival was 27.3% (95% CI 15.6 to 39.0) with high IFN-γ versus 5.6% with lower IFN-γ. Median survival was 14.7 versus 12.8 months (log rank p = 0.050).
  • Training cohort: the other cytokines (TNF, IL-6, IL-10, IL-12p70, IL-1β) were not significantly associated with survival (log rank p values from 0.546 to 0.963).
  • Training cohort, multivariate analysis: high IFN-γ had a hazard ratio for death of 0.49 (95% CI 0.3 to 0.8, p = 0.007). Sarcomatoid versus epithelioid histotype had a hazard ratio of 4.28 (95% CI 2.0 to 9.1). At least one line of therapy had a hazard ratio of 0.30 (95% CI 0.2 to 0.6).
  • Training cohort subgroups: in epithelioid patients, median survival was 20.7 months with IFN-γ above 13.8 pg/ml versus 13.7 months at or below it (p = 0.010). In multivariate analysis, hazard ratios for high IFN-γ were 0.497 in epithelioid patients and 0.324 in treated patients (p = 0.007 and 0.006).
  • Training cohort: reported asbestos exposure was not significantly associated with survival. The univariate hazard ratio for exposed versus unexposed patients was 1.41 (95% CI 0.8 to 2.4), log rank p = 0.176. Median survival was 13.5 months for exposed and 15.8 months for unexposed patients. This analysis concerns survival after diagnosis, not the role of asbestos in causing mesothelioma.
  • Validation cohort of 77: IFN-γ levels showed no relationship with survival.
• The authors' conclusion: The authors concluded that pleural fluid IFN-γ as a prognostic biomarker should be further analyzed in larger prospective cohorts that include balanced numbers of early-stage and late-stage cases.
• Limitations the authors state:
  • The finding could not be validated in the second cohort, where IFN-γ levels were extremely low or undetectable, potentially limiting data reliability.
  • Differences in how samples were handled from collection to storage may explain the discrepant results between cohorts.
  • Tumor stage distribution was unbalanced between the cohorts, with very few stage I to II patients in the validation cohort.
  • IL-12 levels were mostly below detection limits.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cytokine, Exudate, Overall Survival, Kaplan-Meier Curve, Histology, Epithelioid, Pleural Effusion.

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