Novel Murine Pancreatic Tumor Model Demonstrates Immunotherapeutic Control of Tumor Progression by a Toxoplasma gondii Protein
| Autor: | Laura J. Knoll, Nicole M. Davis, Philip B. Emmerich, Dustin A. Deming, Susan N. Payne |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Immunology
Protozoan Proteins Antigens Protozoan Antineoplastic Agents Microbiology Mice Immune system Antigen Pancreatic tumor Cell Line Tumor Pancreatic cancer medicine Animals Biological Products Host Response and Inflammation Tumor microenvironment biology Cancer Allografts medicine.disease Pancreatic Neoplasms Disease Models Animal Infectious Diseases Profilin Tumor progression Cancer research biology.protein Parasitology Toxoplasma |
| Zdroj: | Infect Immun |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00508-21 |
| Popis: | 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 Toxoplasma 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 Kras and P53 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. |
| Databáze: | OpenAIRE |
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