Background

Colorectal cancer is the fourth most common cancer worldwide. Upto 25% of patients have disease that spreads to the peritoneum, which leads to a very poor prognosis. Treatment options for peritoneal disease are very limited, with minimal improvement in survival over the last two decades. Systemic chemotherapy offers modest improvement in survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is effective in very selected patients. However, the majority of patients are not suitable surgical candidates due to very high tumour burden. Immunotherapy, while effective in other cancers, has an undefined role in peritoneal disease.

Methods

Fresh tumour tissue from peritoneal metastases was used for flow cytometry analysis to evaluate immune cell infiltration. Tissue was further processed to develop organoid models. Simultaneous patient matched tumour infiltrative lymphocytes (TILs) were cultured and enriched with interleukin-2 (IL-2). Once organoids were robust and replenishable, they were co-cultured with various concentrations of TILs to assess the cytotoxic ability of the lymphocytes. They were further cultured with TILs with the addition of an anti PD-1 antibody.

Results

Flow cytometry revealed a large CD45 population of mainly T cells. T cells comprised of an even mix of CD4 and cytotoxic CD8 cells. However, 15-20% of CD4 cells were T regulatory cells, which was unexpectedly high. Approximately 20-25% of all T cells had PD-1 expression, suggesting a possible role for anti PD-1 antibody therapy. Co-culture results showed organoid killing increased significantly with the addition of anti PD-1 antibody.

Conclusion

This live assay demonstrates a potential role for immunotherapy in the setting of peritoneal disease. These early results need to be expanded with a larger cohort, and validated in an in-vivo setting.