Changes in the immune tumor microenvironment of peritoneal mesothelioma under intraperitoneal chemotherapy

Abstract Objectives The immunology of peritoneal mesothelioma (PeM) is complex, with the tumor microenvironment (TME) playing a crucial role in disease progression. PeM frequently evades immune detection by altering the TME. Methods This pilot study analyzed archival peritoneal biopsies from three patients with epithelioid PeM treated with intraperitoneal chemotherapy. Using immunohistochemistry and digital image analysis, we evaluated immune cell populations (T cells, B cells, and macrophages) across 19 time points, encompassing 20 histology (HE) sections, 140 immunohistochemistry (IHC) sections, and 1,120 measurement areas. Seven markers quantified immune cell infiltration in the tumor and the peritumoral regions. Results Distinct immune marker patterns in the tumor and TME were identified, suggesting immune cell movement and activity changes at early therapy stages. Key markers, such as CD4 and CD8, exhibited correlated trends between tumor and TME, indicating synchronized immune responses. Early shifts in these markers suggested migration from the tumor to the TME, while CD68 and CD163 showed variable patient-specific patterns, potentially reflecting individual immune responses. Elevated immune marker levels correlated negatively with survival, suggesting advanced disease progression in some cases. Conclusions This study is the first to explore sequential TME changes in PeM under treatment. PeM may evade immune response by modifying the TME, varying among patients. PIPAC’s ability to enable repeated biopsies provides a valuable approach to advancing personalized PeM therapy. Further studies are needed to confirm and specify our findings.