Abstract
Background or Purpose
Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies.
Patients and Methods
Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples.
Results
There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid.
Conclusions
The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.
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Acknowledgments
This work was supported by W81XWH2210009_BC210533 and W81XWH2211069_ BC211396 from the Department of Defense, MetaVivor FP00002718, The Pennsylvania Breast Cancer Coalition, the Glimmer of Hope Foundation, and the David Downing Fund. The Hillman Cancer Center Luminex Facility is supported by Cancer Center Support Grant P30CA047904.
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Wagner, P.L., Knotts, C.M., Donneberg, V.S. et al. Characterizing the Immune Environment in Peritoneal Carcinomatosis: Insights for Novel Immunotherapy Strategies. Ann Surg Oncol 31, 2069–2077 (2024). https://doi.org/10.1245/s10434-023-14553-6
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DOI: https://doi.org/10.1245/s10434-023-14553-6