Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification

Our plain-English summary of Detection of circulating immunosuppressive cytokines in malignant pleural mesothelioma patients for prognostic stratification, by L. Urso, M. Silic-Benussi, A. Boscolo, et al (Cytokine, 2021).

The study

• Authors: L. Urso, M. Silic-Benussi, A. Boscolo, M. Lorenzi, L. Bonanno, F. Lunardi, V. Guarneri, F. Calabrese, F. Rea, P. Conte, G. Pasello
• Journal: Cytokine
• Published: 2021;146:155622
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: No data on circulating biomarkers for the prognostic stratification of Malignant Pleural Mesothelioma (MPM) patients are available. We prospectively explored the prognostic role of circulating monocyte and cytokine levels and their dynamic change during chemotherapy.

Patients And Methods: MPM patients receiving a first line treatment based on a platinum compound plus pemetrexed were eligible. Blood samples were collected at the baseline and at the end of induction chemotherapy. CCL-2, IL-10 and TGF-β levels in plasma were quantified by Enzyme-Linked Immunosorbent Assay (ELISA); white blood cells, monocytes and platelets were evaluated by blood count test.

Results: Thirty-one patients were included in the study. Median overall survival (OS) was 12.13 months versus 9.6 months in patients with lower and higher monocytes count, respectively (p value = 0.02). We further stratified patients according to a combined score based on the association of IL-10, TGF-β levels and monocytes count. High combined score was associated with shorter OS and PFS in univariate and multivariate analysis. Chemotherapy induced an increase in monocytes, IL-10, but not TGF-β levels.

Conclusion: The prognostic value of circulating levels of multiple immunosuppressive cytokines and inflammatory cells should be confirmed in a wider validation set of MPM patients.

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

In plain English

This short communication reported a single-centre prospective study of 31 patients with malignant pleural mesothelioma treated at the Istituto Oncologico Veneto in Padua, Italy, between April 2018 and November 2020. All received first-line platinum plus pemetrexed chemotherapy. The authors measured three immune signalling proteins (CCL-2, IL-10 and TGF-β) in blood plasma and counted monocytes, a type of white blood cell. They did this before chemotherapy and, in 23 patients, again afterwards. Asbestos exposure was not examined. Median overall survival was 12.13 months in patients with lower monocyte counts versus 9.6 months in those with higher counts (p value 0.02). Higher TGF-β and IL-10 levels showed a trend toward worse survival that was not statistically significant. A combined score built from monocytes, IL-10 and TGF-β was associated with shorter survival (p value 0.007), including in multivariate analysis, and with shorter time before the disease progressed. After chemotherapy, IL-10 rose (p value 0.03) but TGF-β did not. The authors named the small sample size as the main weakness and described their results as preliminary findings.

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: Single-centre prospective study of consecutive patients (published as a short communication)
• Who was studied: 31 patients with malignant pleural mesothelioma at the Istituto Oncologico Veneto, Padua, Italy, April 2018 to November 2020. Median age at diagnosis was 74 years (range 44 to 83), and 27 (87%) had epithelioid histology. All had blood sampled before chemotherapy; 23 had a second sample at the end of induction chemotherapy.
• Exposure: Not asbestos. The study examined blood levels of CCL-2, IL-10 and TGF-β, and monocyte and other blood cell counts, measured before and after first-line platinum (cisplatin or carboplatin) plus pemetrexed chemotherapy.
• Main results:
  • Median overall survival was 12.13 months in patients with lower monocyte counts versus 9.6 months in patients with higher monocyte counts (p value 0.02).
  • Patients with higher TGF-β and IL-10 levels showed a trend toward worse survival, but it was not statistically significant.
  • A high combined score (at least two of monocytes, IL-10 and TGF-β above the median) was associated with shorter overall survival: median 12.13 (low score) versus 9.6 (high score), p value 0.007. The effect was confirmed in multivariate analysis (p value 0.026).
  • Shorter progression-free survival was associated with a high baseline monocyte count (median 11.2 versus 5.8 months for low and high counts, p value 0.015) and with a high combined score (median 9.4 versus 4.5 months, p less than 0.001).
  • CCL-2 levels and the neutrophil-to-lymphocyte ratio showed no correlation with survival. Baseline cytokine and monocyte levels showed no correlation with response to treatment or disease load.
  • In paired samples taken before and after chemotherapy, IL-10 increased (p value 0.03) but TGF-β did not (p value 0.43). The total monocyte count did not significantly increase, but the percentage of monocytes among white blood cells was higher after chemotherapy (p value 0.007).
• The authors' conclusion: The authors described their results as preliminary findings and said the prognostic value of these blood markers should be confirmed in a wider validation set of patients, which they reported is under investigation.
• Limitations the authors state:
  • The authors named the small sample size as the main weakness, saying it limits the strength of the findings.
  • The authors observed no impact of stage, surgery, radiation therapy or further treatments on survival. They suggested this may reflect the small number of patients and their varied treatment pathways.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytokine, Pleural Mesothelioma, Biomarker, Chemotherapy, Pemetrexed (Alimta), Median Overall Survival, Multivariate Analysis.

Related studies

• Detection of TGF-β in pleural effusions for diagnosis and prognostic stratification of malignant pleural mesothelioma — P. Stockhammer, T. Ploenes, et al. (2020)
• Asbestos stimulation triggers differential cytokine release from human monocytes and alveolar macrophages — L.J. Geist, L.S. Powers, et al. (2000)
• Intraperitoneal cytokine level in patients with peritoneal surface malignancies. A study of the RENAPE (French Network for Rare Peritoneal Malignancies) — V. Vlaeminck-Guillem, J. Bienvenu, et al. (2013)
• Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin — G. Ak, Y. Tada, et al. (2017)
• Presence of pleomorphic features but not growth patterns improves prognostic stratification of epithelioid malignant pleural mesothelioma by 2-tier nuclear grade — Y.Z. Zhang, C. Brambilla, et al. (2020)
• Droplet digital PCR as a novel system for the detection of microRNA‑34b/c methylation in circulating DNA in malignant pleural mesothelioma — H. Sato, J. Soh, et al. (2019)

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