The Tumor Environment in Peritoneal Carcinomatosis and Malignant Pleural Effusions: Implications for Therapy

Our plain-English summary of The Tumor Environment in Peritoneal Carcinomatosis and Malignant Pleural Effusions: Implications for Therapy, by P.O. Mirsky, P.L. Wagner, M. Mandic-Popov, et al (Cancers, 2025).

The study

• Authors: P.O. Mirsky, P.L. Wagner, M. Mandic-Popov, V.S. Donnenberg, A.D. Donnenberg
• Journal: Cancers
• Published: 2025;17(19)
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common complications of cancers metastatic to the respective body cavities. A PC diagnosis indicates metastasis to the tissue lining the abdominal cavity and is most common in patients with gastrointestinal and gynecological cancers. It is often accompanied by ascites, an accumulation of serous fluid in the abdomen. MPE presents as the accumulation of fluid in the space between the lungs and chest wall. It is a common terminal event in patients diagnosed with breast cancer, lung cancer, lymphoma, and mesothelial cancers, and less commonly, in a wide variety of other epithelial cancers. Due to the aggressive nature of cavitary tumors, the outcome of current treatments for both PC and MPE remains bleak. Although PC and MPE are characteristically affected by different sets of primary tumors (lung/breast/mesothelioma for MPE and gynecologic/gastrointestinal for PC), their environments share common cytokines and cellular components. Owing to the unique cytokine and chemokine content, this environment promotes aggressive tumor behavior and paradoxically both recruits and suppresses central memory and effector memory T cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective but also invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity. Interactions between the heterogeneous components of the tumor environment are an area of active research. We highlight the roles of the immune cell infiltrate, stromal cells, and tumor cells, and the soluble products that they secrete into their environment. A more comprehensive understanding of the cavitary tumor environment can be expected to lead to better immunotherapeutic approaches to these devastating conditions.

In plain English

This article is a review; the authors stated that no new data were created or analyzed. It described the environment inside the abdominal and chest cavities when cancer spreads there (peritoneal carcinomatosis and malignant pleural effusions), and discussed immune-based treatments. It does not discuss asbestos. Drawing on earlier research, it described these fluids as containing IL-10, TGFβ, IL-1RA and IL-6 signaling, which the authors linked to suppressed immunity against tumors. The authors wrote that evidence suggests T cells there are resting rather than exhausted and can be reactivated. Malignant pleural mesothelioma was one of several cancers discussed. The review cited reports that effusion occurs in up to 90% of these patients. It also cited a 30-patient study linking higher effusion TGFβ to more advanced stage and poor survival. It also cited a report of mesothelin-targeted CAR-T cells given into the chest: of 21 treated patients, 14 also received anti-PD-1 therapy, and two had a complete metabolic response on PET CT after combination therapy. The authors concluded that preclinical and clinical data justify continued development of biomarkers and treatments aimed at this environment.

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 research; no new data
• Who was studied: Published research on peritoneal carcinomatosis and malignant pleural effusions from a range of cancers, including lung, breast, gastrointestinal and gynecological cancers and malignant pleural mesothelioma
• Exposure: Not applicable: the article does not discuss asbestos or any fiber exposure. It reviews immune and cytokine features of cavity tumors and immune-based and cellular therapies.
• Main results:
  • The review described the malignant cavity environment as containing the immunosuppressive cytokines IL-10, TGFβ and IL-1RA, with amplification of the IL-6/soluble IL-6Rα axis
  • The authors stated that, based on the evidence they reviewed, T cells infiltrating these cavities appear quiescent rather than exhausted and can be reactivated by cytokines such as IL-2
  • Citing earlier work, the review stated that malignant pleural effusion is found in up to 90% of patients with malignant pleural mesothelioma
  • Citing a study of 30 patients with malignant pleural mesothelioma, the review reported that TGFβ concentrations were significantly higher in malignant pleural effusion samples than in non-malignant effusion samples. Higher TGFβ was correlated with more advanced disease staging and poor survival.
  • Citing work on mesothelin-targeted CAR-T cells delivered into the pleura for malignant pleural mesothelioma, the review reported 21 treated patients. Of these, 14 also received anti-PD-1 therapy, and two achieved a complete metabolic response on PET CT after combination therapy.
  • The authors reported that their own earlier research did not detect regulatory T cells among pleural infiltrating T cells in breast cancer. Other cited studies reported increased regulatory T cells in malignant effusions.
• The authors' conclusion: The authors concluded that this cavity environment is largely responsible for the poor prognosis of cavity cancers. They stated that preclinical and clinical data justify continued development of biomarkers to identify patients who respond, drugs targeting the PC and MPE environment, and approaches that use the immune cell infiltrate.
• Limitations the authors state:
  • The authors noted limited data supporting single-agent anti-PD-1 antibodies given directly into the cavity
  • The authors noted that most efficacy data for CAR-T treatment in cancers with PC or MPE come from animal models

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Metastasis, Ascites, Serous Fluid, Lung Cancer, Mesothelioma, Cytokine.

Related studies

• Preoperative Circulating Tumor DNA in Patients with Peritoneal Carcinomatosis is an Independent Predictor of Progression-Free Survival — J.M. Baumgartner, V.M. Raymond, et al. (2018)
• 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)
• Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis — N. Dadgar, C. Sherry, et al. (2024)
• Cytotoxicity assessment of some carbon nanotubes and related carbon nanoparticle aggregates and the implications for anthropogenic carbon nanotube aggregates in the environment — L.E. Murr, K.M. Garza, et al. (2005)
• Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence — W.P. Ceelen, M.F. Flessner (2010)
• Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy — G. Glockzin, H.J. Schlitt, et al. (2009)

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