The Anti-tumor Effect and Immunological Cell Changes of PRaG Therapy in Colon Cancer Peritoneal Metastasis of Mice

Backgrounds To illustrate the anti-tumor effect of PRaG therapy in the peritoneal metastasis of colon cancer in mice and explore the immunological cell changes involved provide reference for PRaG clinical research.

Methods The CT26.WT colon cancer cells were subcutaneously and intraperitoneally inoculated in BALB/c mice, to construct a subcutaneous tumor peritoneal metastasis model. The mice were divided into control group (CON), PD-1 inhibitor group (P), radiotherapy group (Ra), PD-1 inhibitor and radiotherapy group (PRa), PD-1 inhibitor, radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) group (PRaG). Caliper was used to measure the long and short diameter of the subcutaneous tumor to calculate the tumor volume. Ethical death standards were set with tumor volume >1,500 mm³, and the survival period of mice was recorded. Flow cytometry was employed to detect and analyze the differences of T cell percentage and phenotype, and myeloid-derived suppressor cell (MDSCs) subgroups in peripheral blood across different treatment groups.

Results Compared with CON and P groups, the PRaG group showed significantly reduced subcutaneous tumor volume (P < 0.01). Compared with CON and PRa groups, the PRaG group had more extended survival period (P < 0.05). In peripheral blood, the PRaG group had reduced CD4⁺ T cell percentage compared with the CON, Ra, and PRa groups (P < 0.05). G-MDSC percentage decreased obviously in PRaG group compared to CON and Ra groups (P < 0.05).

Conclusions In the subcutaneous tumor peritoneal metastasis model of colorectal cancer, compared with the combined radiotherapy and PD-1 inhibitor, PRaG therapy has more significant anti-tumor effect. The specific cellular mechanisms may be related to the reduction of CD4⁺ T cells in peripheral blood.