A genetic inference on cancer immune responsiveness

Abstract

A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness.

Figure 1. Interplay among categorical modifiers of responsiveness. (A) Classical view of the relationship between host genetic background, tumor genetics and environmental factors. (B) A more likely scenario integrating the large overlap between the genetics of the host and the tumor and the over-reaching effect of environmental factors on both of them.

Figure 2. Check point regulating the winding road to cancer immune responsiveness. The host’s genetic may be the first limiting factor and a genetic predisposition to immune response may be necessary but not sufficient to allow cancer response to immunotherapy. Subsequently, genetic alteration of cancer cells may allow escape from immune recognition in spite of a favorable genetic background. Finally, quality and intensity of treatment and a myriad of hidden external factors may determine the final outcome.

Figure 3. A quantitative continuum determining the responsiveness of tumors according to genetic background of the host, genetics of cancer cells, effectiveness of treatment and other “hidden” external factors that may affect the final outcome.