Immune modulation in malignant pleural effusion: from microenvironment to therapeutic implications

Our plain-English summary of Immune modulation in malignant pleural effusion: from microenvironment to therapeutic implications, by S. Ge, Y. Zhao, J. Liang, et al (Cancer Cell International, 2024).

The study

• Authors: S. Ge, Y. Zhao, J. Liang, Z. He, K. Li, G. Zhang, B. Hua, H. Zheng, Q. Guo, R. Qi, Z. Shi
• Journal: Cancer Cell International
• Published: 2024;24(1):105
• Type of article: Review
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Immune microenvironment and immunotherapy have become the focus and frontier of tumor research, and the immune checkpoint inhibitors has provided novel strategies for tumor treatment. Malignant pleural effusion (MPE) is a common end-stage manifestation of lung cancer, malignant pleural mesothelioma and other thoracic malignancies, which is invasive and often accompanied by poor prognosis, affecting the quality of life of affected patients. Currently, clinical therapy for MPE is limited to pleural puncture, pleural fixation, catheter drainage, and other palliative therapies. Immunization is a new direction for rehabilitation and treatment of MPE. The effusion caused by cancer cells establishes its own immune microenvironment during its formation. Immune cells, cytokines, signal pathways of microenvironment affect the MPE progress and prognosis of patients. The interaction between them have been proved. The relevant studies were obtained through a systematic search of PubMed database according to keywords search method. Then through screening and sorting and reading full-text, 300 literatures were screened out. Exclude irrelevant and poor quality articles, 238 literatures were cited in the references. In this study, the mechanism of immune microenvironment affecting malignant pleural effusion was discussed from the perspectives of adaptive immune cells, innate immune cells, cytokines and molecular targets. Meanwhile, this study focused on the clinical value of microenvironmental components in the immunotherapy and prognosis of malignant pleural effusion.

© 2024. The Author(s).

In plain English

This article was a review. The authors searched PubMed, in English only, for research on the immune environment of malignant pleural effusion. This is fluid around the lungs caused by cancers such as lung cancer and malignant pleural mesothelioma. They summarized earlier work on immune cells, signaling molecules and immunotherapies. They also searched asbestosis or erionite with immune topics, including 16 asbestos-related articles. The asbestos section described earlier laboratory work. When crocidolite or chrysotile fibers were added to cytokine-stimulated cultures, rat alveolar macrophages made more nitric oxide. Inhaled chrysotile and amosite produced proliferative lesions in rat airway and proximal alveolar epithelium. It also described asbestos exposure leading cells to release a protein called HMGB1. The review noted that impaired T-cell function is not necessarily found with asbestos-associated cancer. Among treatment studies, it described a cited trial of 605 malignant pleural mesothelioma patients. In that trial, nivolumab plus ipilimumab gave a median survival of 18.1 months, versus 14.1 months with chemotherapy. The authors concluded there is no definite basis yet for immunotherapy to replace traditional therapies in the short term.

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: Narrative review of published literature identified through a PubMed search and a manual search of reference lists
• Who was studied: Published English-language articles on the immune microenvironment and immunotherapy of malignant pleural effusion (MPE). These included reviews, cell, animal and clinical sample studies, and clinical trials. After title and abstract screening, 224 articles went to full-text analysis.
• Exposure: The review mainly covered immune cells, cytokines and molecular targets in MPE. A separate search covered asbestosis or erionite and immunity. The asbestos fibers named in the reviewed work were crocidolite, chrysotile and amosite; erionite was also named.
• Main results:
  • 16 asbestos-related articles were included in the review
  • The review described earlier studies in which crocidolite or chrysotile fibers were added to cytokine-stimulated cell cultures. This increased nitric oxide production by rat alveolar macrophages and by rat parietal pleural mesothelial cells.
  • The review cited studies in which inhalation of chrysotile and amosite produced proliferative lesions in rat airway and proximal alveolar epithelium
  • The review cited work finding that, on asbestos exposure, HMGB1 is released by reactive macrophages, by other inflammatory cells and by human mesothelial cells
  • The review stated that impaired T-cell function is not necessarily a common finding with asbestos-associated malignancy
  • A cited randomized study enrolled 605 malignant pleural mesothelioma (MPM) patients to compare nivolumab plus ipilimumab with chemotherapy
  • In that cited MPM trial, nivolumab plus ipilimumab was compared with platinum and pemetrexed chemotherapy. Median survival was 18.1 versus 14.1 months, and the 2-year overall survival rate was 41% versus 27%.
  • A cited study combined dendritic cells with low-dose cyclophosphamide in MPM and reported disease control in 8 of 10 patients
  • A cited study found that NK cells in the effusions of MPM patients showed high TIM-3 and LAG-3 expression
• The authors' conclusion: The authors concluded that there is not yet a definite basis for immunotherapy to replace traditional therapies in the short term. They added that study of tumour immune mechanisms offers new directions for clinical practice.
• Limitations the authors state:
  • The authors did not describe limitations of their own review. They did state a gap in current knowledge: limited understanding of the tumour microenvironment hinders the development of new immunotherapy targets.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Immunotherapy, checkpoint inhibitors, Lung Cancer, Pleural Mesothelioma, Prognosis, Quality of Life, Palliative Care.

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• Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy — J. Harber, T. Kamata, et al. (2021)
• The role of PCMT1 in prognosis tumor immune microenvironment and therapeutic responses across cancers — B. Wang, S. Huang, et al. (2026)
• Reprogramming the tumor microenvironment in mesothelioma: from immune suppression to therapeutic opportunity — L. Cerbone, A. Garau, et al. (2026)
• Dynamic evolution of NK cells and immune remodeling mediated by CRS + HIPEC: prognostic mechanisms and therapeutic implications for malignant peritoneal mesothelioma — Y.T. Liu, Q.D. Zhao, et al. (2025)
• Secretome of pleural effusions associated with non-small cell lung cancer (NSCLC) and malignant mesothelioma: therapeutic implications — A.D. Donnenberg, J.D. Luketich, et al. (2019)

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