Tripartite treatment by radiation, hyperthermia and anti-OX40 immunotherapy potentiates tumor growth delay and tumor microenvironment immunomodulation in pancreatic cancer

Abstract

Pancreatic cancer is the fourth most deadly cancer in the United States. Despite development in conventional treatment strategies the 5 year survival rate is only 7.7%. In this study we demonstrated that the tripartite treatment by combination of fractionated radiation therapy, hyperthermia and anti-OX40 immunotherapy (tripartite) led to significant impact on pancreatic cancer in mice. The treatment of mice with the tripartite treatment demonstrated significant tumor growth inhibition (p<0.0001) with no observable toxicity due to this treatment. Flow cytometric analysis of the tumor showed a shift in tumor microenvironment from immune suppressive to immune stimulatory with significantly higher CD4+ and CD8a+ (p<0.05) T lymphocytes. A significantly higher population of helper T cells and cytotoxic T cells was observed in the usually immune-deficient pancreatic cancer tumor microenvironment coupled with a decrease in the immunosuppressive microenvironment in the tumors of animals receiving the tripartite treatment is potentially the cause of the superior anti-tumor effect observed in animals receiving the tripartite treatment.