Australian researchers have discovered that peritoneal mesothelioma develops in an immune-suppressive tumor microenvironment that makes it resistant to checkpoint immunotherapy. These findings explain the significant difference between pleural mesothelioma and peritoneal mesothelioma patients observed in clinical trials.
Mesothelioma Location Influences Immune Response and Treatment Effectiveness
The study, published in Scientific Reports, compared identical mesothelioma cells implanted in three different anatomical locations in mice: the pleural cavity, the abdominal cavity, and under the skin. The research showed that the peritoneal location actually created a tumor microenvironment and a gene signature typical of limited response to immune checkpoint therapy.
While the immune checkpoint therapy was effective in the mesothelioma cells implanted subcutaneously, the same cell line-derived tumors were unresponsive when implanted intraperitoneally. This demonstrates that anatomical location fundamentally alters treatment outcomes. While pleural and peritoneal mesothelioma tumors grew to similar sizes, subcutaneous tumors were significantly smaller when harvested at the same time point.
Both the peritoneal and pleural mesothelioma tumors invaded nearby organs early, with peritoneal tumors spreading to the pancreas and liver, and pleural tumors invading the heart and diaphragm, but the pleural tumors showed more immune cells clustering around them compared to the peritoneal tumors, meaning that the immune system responded more actively to mesothelioma in the chest than in the abdomen.
Mesothelioma Immune Microenvironment Differences Suggest Combination Therapy Strategies
The research suggests that future mesothelioma treatments may need to combine immunotherapy with other drugs that “wake up” or reprogram inactive immune cells in the abdomen. Recent studies have shown that drugs can shift the immune system from tumor-supporting to tumor-fighting, which suggests that this type of combination strategy may be able to overcome the immunotherapy resistance seen in peritoneal mesothelioma patients.
The study’s results show that where mesothelioma tumors grow—the chest versus the abdomen—has a significant influence on how the immune system responds and whether immunotherapy will work. This explains both why peritoneal mesothelioma patients need different treatment approaches than those with pleural tumors, and suggests potential approaches to offset this difference.
If you or someone you love has been diagnosed with mesothelioma, this type of research helps provide better outcomes. If you need more information or access to helpful resources, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.
