Cancer immunotherapy through the prism of the adaptation concept: will Achill catch up with the turtle?

Abstract

Immunotherapy provides significant progress in treatment of cancer although not for all and not always. In this review, we briefly analyzed major immunotherapies for cancer and outlined a new approach to improve their effectiveness. We examined the issue of cancer immunotherapy through the prism of the concept of adaptation to environmental factors. In the context of this concept, the high survival rate of tumor cells may be due to cell adaptation to drugs and aggressive immunity factors, such as free radicals and inflammatory cytokines. In the oncological clinic, physicians try to enhance the patient’s immunity with immunotherapy. This tactic is warranted if the physician would manage to increase the potency of immune attack to a level that kills the tumor. However, if the enhanced power of immunity attack is insufficient to kill a tumor cell, the tumor may additionally adjust and stabilize. Therefore, a clinically important hypothesis ensues: the tumor cell survival may be impaired by disrupting its adaptive mechanisms. The concept of adaptation offers two options: 1) to block activated synthesis of the genes and proteins that are required for formation of an adaptive systemic structural trace (SST) and 2) to stop the action of adapting factors, and, thereby, to erase the SST and induce maladaptation with loss of the acquired resistance of the tumor. With regard to cancer immunotherapy, the second option creates, at the first glance, an absurd idea, to “turn off” the immune system for a period preceding the stage of tumor maladaptation, and only then to apply immunotherapy to the tumor cells that have become less resistant. This hypothesis needs to be verified but some indirect data are already consistent with it. Reducing the adaptive resistance of tumor cells could significantly increase the antitumor potential of cancer immunotherapy.