The role of cytokines in the evolution of cancer: IFN-γ paradigm.

The evolution of malignant cells implies an increase in oncogenic fitness of cells which arises in active and reciprocal interaction with the tumor microenvironment. The mechanisms facilitating the adaptive evolution of cancer cells involve clonal selection of cancer cells, in a direction of increased adaptive potential under the selective pressure of host defensive strategies. Once reached, this potential could go the other way, changing the same evolutionary force in the tumor microenvironment which influenced its emergence and favoring cancer progression. The immunological system as a part of host defensive mechanisms could be an effective modulator of cancer evolution/progression since it is also a major source of cellular intermediators, such as cytokines. The exemplar of IFN-γ actions during cancer evolution could help the revealing of these mutual interactions and enable better insight into the complex nature of cancer disease, leading to a new approach to treatment strategies.