Details

Autor(en) / Beteiligte

• Payne, Susan N
• Emmerich, Philip B
• Davis, Nicole M
• Deming, Dustin A
• Knoll, Laura J
• Saeij, Jeroen P. J
• Saeij, Jeroen P. J.

Titel

Novel Murine Pancreatic Tumor Model Demonstrates Immunotherapeutic Control of Tumor Progression by a Toxoplasma gondii Protein

Ist Teil von

• Infection and immunity, 2021-11, Vol.89 (12), p.e0050821-e0050821

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer-related death in the United States, with few effective treatments available and only 10% of those diagnosed surviving 5 years. Although immunotherapeutics is a growing field of study in cancer biology, there has been little progress in its use for the treatment of pancreatic cancer. Pancreatic cancer is considered a nonimmunogenic tumor because the tumor microenvironment does not easily allow for the immune system, even when stimulated, to attack the cancer. Infection with the protozoan parasite Toxoplasma gondii has been shown to enhance the immune response to clear cancer tumors. A subset of T. gondii proteins called soluble antigen (STAg) contains an immunodominant protein called profilin. Both STAg and profilin have been shown to stimulate an immune response that reduces viral, bacterial, and parasitic burdens. Here, we use STAg and profilin to treat pancreatic cancer in a KPC mouse-derived allograft murine model. These mice exhibit pancreatic cancer with both and mutations as subcutaneous tumors. Pancreatic cancer tumors in C57BL/6J mice with a wild-type background showed a significant response to treatment with either profilin or STAg, exhibiting a decrease in tumor volume accompanied by an influx of CD4 and CD8 T cells into the tumors. Both IFN-γ mice and Batf3 mice, which lack conventional dendritic cells, failed to show significant decreases in tumor volumes when treated. These results indicate that gamma interferon (IFN-γ) and dendritic cells may play critical roles in the immune response necessary to treat pancreatic cancer.