- A mathematical model of pancreatic cancer development and the immune response
- Project Year:
2020
- REU Student (s):
Chloe Shiff | Brandeis University MA
- Student 1 Institution:
Brandeis University
- Project Mentor:
Subhajyoti De
- Project Mentor Area:
Rutgers Cancer Institute of New Jersey
- Project Abstract:
Although tumors arise as a result of the rapid proliferation of cancerous cells, these cells comprise only a fraction of the tumor. Many types of cells, each of which possesses a specific role in the growth of solid tumors, make up the tumor microenvironment (TME). In recent years, immunotherapy, a treatment that utilizes the significant presence of immune cells within the TME, has proven effective for liquid tumors such as leukemia and lymphoma. However, in solid tumors, the complex relationships within the TME can make the response to immunotherapy challenging to predict and the treatment difficult to use effectively. Thus, we created a mathematical model of pancreatic adenocarcinoma growth which includes cancer cells, T-cells, and macrophages, and used it to study the dynamics of the cellular interactions within the TME over time and throughout treatment. The model behavior indicates that the ability of CAR T-cells to kill cancer cells is more critical than their persistence. However, when used in combination with chemotherapy, the tumor can be eliminated using less effective T-cells than would be needed if using immunotherapy alone. These results indicate that CAR T-cell research should focus on engineering T-cells with high efficacy in killing cancer cells rather than long persistence in the body. Doing so could allow for effective immunotherapy use in solid tumors, either as a lone treatment or used in combination with chemotherapy.
