Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients

Our plain-English summary of Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients, by N. Fusco, V. Vaira, I. Righi, et al (Lung Cancer, 2020).

The study

• Authors: N. Fusco, V. Vaira, I. Righi, E. Sajjadi, K. Venetis, G. Lopez, M. Cattaneo, M. Castellani, L. Rosso, M. Nosotti, M. Clerici, S. Ferrero
• Journal: Lung Cancer
• Published: 2020;150:53-61
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is a rare tumor with an extremely poor prognosis. Its pathogenesis is related to an immune response against asbestos fibers. The T-lymphocytes, including CD8POS and CD4POS cells, are an important part of the MPM immune microenvironment, and likely contribute to the therapy resistance observed in these tumors. Here, we sought to characterize the MPM-specific lymphocytes subpopulations within the tumor immune microenvironment to identify novel clinically relevant immunologic subtypes of tumors. Representative formalin-fixed, paraffin-embedded (FFPE) tissue blocks of 88 MPMs were included in tissue microarrays and subjected to tumor-infiltrating lymphocytes (TILs) quantification and subtyping by immunohistochemistry (IHC) with antibodies specific for CD4, CD8, and CD19. Further, PD-L1 (clone 22C3) expression was assessed by IHC as a combined positive score (CPS). Our data show that PD-L1 expression by tumor cells or the presence of a sarcomatoid component is related to increased stromal TILs presence in MPM. Survival analyses showed that low CD4POS and high CD8POS stromal TILs are associated with poor patients' survival. In MPMs with PD-L1 CPS > 1, stromal CD8HIGH was a poor prognostic factor, akin stromal CD4POS peritumoral TILs correlated with a worse prognosis. Furthermore, we demonstrated that a high CD4POS/CD8POS ratio in the tumor immune microenvironment is an independent prognostic factor for survival. Finally, we provided evidence that the characterization of the stromal immune landscape of MPM predicts responses to chemotherapy in subgroups of MPM. The results of this study provide novel insights into the clinical scenario of immune-related biomarkers in MPM.

Copyright © 2020 Elsevier B.V. All rights reserved.

In plain English

This study, from a hospital in Milan, Italy, examined tumor tissue from 88 people with malignant pleural mesothelioma. They were drawn from 118 patients enrolled between 2008 and 2016. The authors stained the tissue to measure immune cells (CD4, CD8 and CD19 lymphocytes) and the protein PD-L1, then compared these measurements with survival. Forty-five of the 88 patients had recorded asbestos exposure. The authors found no correlation between immune-cell levels and asbestos exposure. Low CD4 levels (under 25%) and high CD8 levels (over 65%) in immune cells inside the tumor were associated with poorer survival. In a combined analysis, a CD4-to-CD8 ratio above 1 was linked to a lower risk of death, with a hazard ratio of 0.0620 (95% confidence interval 0.0206 to 0.1868). Among patients given chemotherapy, 44 of 64 (69%) survived more than a year, compared with 7 of 21 (33%) who were not. The authors concluded that the immune makeup of these tumors identifies prognostic subgroups. They noted that small tissue samples may miss variation within a tumor and that further studies are needed.

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 laboratory study of archived tumor tissue (tissue microarrays stained by immunohistochemistry), linked to patients' clinical and survival data
• Who was studied: 88 of 118 patients with malignant pleural mesothelioma at Fondazione IRCCS Ca' Granda, Milan, Italy, who had enough tumor tissue. The 88 comprised 54 epithelioid, 5 sarcomatoid and 29 biphasic tumors, and 59 of the patients (67%) were male.
• Exposure: The study measured immune cells in the tumor (CD4, CD8 and CD19 lymphocytes) and PD-L1 expression. Asbestos exposure was recorded for 45 of 88 patients (51%). No fiber types or doses are given.
• Main results:
  • PD-L1 (combined positive score of 1 or more) was found in 16 of 54 epithelioid, 2 of 5 sarcomatoid and 9 of 29 biphasic tumors.
  • No correlation was observed between immune-cell (TIL) levels and asbestos exposure.
  • Among immune cells inside the tumor, CD19 and CD4 cells were significantly more common in tumors with a sarcomatoid component (p = 0.02 and p = 0.01).
  • For all 88 patients, low CD4 (under 25%) and high CD8 (over 65%) immune cells inside the tumor were associated with poorer survival.
  • In the multivariate analysis, a stromal CD4-to-CD8 ratio above 1 had a hazard ratio of 0.0620 (95% CI 0.0206 to 0.1868), with p less than 0.0001.
  • In patients whose tumors were PD-L1 positive, high stromal CD8 was a poor prognostic factor.
  • 44 of 64 chemotherapy-treated patients (69%) survived more than one year, compared with 7 of 21 (33%) who did not receive chemotherapy (p = 0.005).
• The authors' conclusion: The authors concluded that their data provide insights into the immune biology of malignant pleural mesothelioma and support further studies on whether patients might benefit from immune checkpoint inhibitors.
• Limitations the authors state:
  • Tissue microarrays are not a gold standard because tumors vary internally.
  • Surgery was mostly diagnostic, so only a few nodules were sampled and the percentage of sarcomatoid component was not recorded.
  • The chemotherapy findings might also depend on patients' clinical factors.
  • Further studies are needed to validate the findings.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Paraffin Block, Tumor-Infiltrating Lymphocytes, Immunohistochemistry, PD-L1, Sarcomatoid, Chemotherapy.

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• Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma — A.N. Qualiotto, C.M. Baldavira, et al. (2023)
• Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma — F. Napoli, A. Listì, et al. (2021)
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