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The Tumor Environment in Peritoneal Carcinomatosis and Malignant Pleural Effusions: Implications for Therapy
Journal article   Open access   Peer reviewed

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

Paige O. Mirsky, Patrick L. Wagner, Maja Mandic-Popov, Vera S. Donnenberg and Albert D. Donnenberg
Cancers, v 17(19), 3217
02 Oct 2025
PMID: 41097743
url
https://doi.org/10.3390/cancers17193217View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Science & Technology Oncology
Simple Summary Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common manifestations of metastatic cancer. The native cavitary immune environment and the metastatic tumor interact in ways that promote aggressive tumor behavior, both recruiting and suppressing immune cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective. The unique cavitary tumor environment invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity.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.

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This publication has contributed to the advancement of the following goals:

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