Pancreatic cancer is one of the most deadly types of cancer and has extremely poor prognosis. This malignancy typically induces only limited cellular immune responses, the magnitude of which can increase with the number of encountered cancer cells. On the other hand, pancreatic cancer is highly effective at evading immune responses by inducing polarization of pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages, and promoting expansion of myeloid derived suppressor cells, which block the killing of cancer cells by cytotoxic T cells. These factors allow immune evasion to predominate, promoting metastasis and poor responsiveness to chemotherapies and immunotherapies. In this paper we develop a mathematical model of pancreatic cancer, and use it to qualitatively explain a variety of biomedical and clinical data. The model shows that drugs aimed at suppressing cancer growth are effective only if the immune induced cancer cell death lies within a specific range, that is, the immune system has a specific window of opportunity to effectively suppress cancer under treatment. The model results suggest that tumor growth rate is affected by complex feedback loops between the tumor cells, endothelial cells and the immune response. The relative strength of the different loops determines the cancer growth rate and its response to immunotherapy. The model could serve as a starting point to identify optimal nodes for intervention against pancreatic cancer.
Bibliographical noteFunding Information:
This work is partially supported by the Mathematical Biosciences Institute at the Ohio State University . CX is supported in part by the National Science Foundation in the United States through Grant DMS 1312966 . GBL is supported by NIH Grants 1R01 CA169363-01 and 1R21 CA173473-01 , and research funding from Prometheus, Inc. , Karyopharm Therapeutics, Inc. , Oncolytics, Inc. , Array Biopharma, Inc. and Bristol Myers-Squibb, Inc.
- Immune response
- Pancreatic cancer