Wednesday, May 29, 2013

Modeling the Dichotomy of the Immune Response to Cancer: Cytotoxic Effects and Tumor-Promoting Inflammation

Modeling the Dichotomy of the Immune Response to Cancer: Cytotoxic Effects and Tumor-Promoting Inflammation
Kathleen P. WilkiePhilip Hahnfeldt
 (Wed, 15 May 2013 20:58:57)

Although the immune response is often regarded as acting to suppress tumor growth, it is now clear that it can be both stimulatory and inhibitory. The interplay between these competing influences has complex implications for tumor development and cancer dormancy. To study this biological phenomenon theoretically we construct a minimally parameterized framework that incorporates all aspects of the immune response. We combine the effects of all immune cell types, general principles of self-limited logistic growth, and the physical process of inflammation into one quantitative setting. Simulations suggest that while there are pro-tumor or antitumor immunogenic responses characterized by larger or smaller final tumor volumes, respectively, each response involves an initial period where tumor growth is stimulated beyond that of growth without an immune response. The mathematical description is non-identifiable which allows us to capture inherent biological variability in tumor growth that can significantly alter tumor-immune dynamics and thus treatment success rates. The ability of this model to predict immunomodulation of tumor growth may offer a template for the design of novel treatment approaches that exploit immune response to improve tumor suppression, including the potential attainment of an immune-induced dormant state.