Cancer immunotherapy through the prism of adaptation: Will Achilles catch the tortoise?

• Published in: Medical hypotheses 2020-04, Vol.137, p.109545, Article 109545
• Main Authors: Malyshev, Igor Y., Kuznetsova, Larisa V., Mardente, Stefania
• Format: Article
• Language: English
• Subjects: Animals; Immune Tolerance; Immunologic Factors; Immunotherapy; Neoplasms - therapy; Turtles
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2019.109545

There is no secret that despite the rapid development of new methods of cancer therapy, we still are not able to completely destroy the tumor. Every time we attack the tumor, the tumor neutralizes our attempts. Carcinogenesis can be presented as a tree whose branches are different pro-tumor mechanisms and whose trunk is a biological phenomenon that “feeds” those branches. A tree can be destroyed in two ways: either by cutting a branch for a branch without a guarantee that new branches will not grow, or cutting down the trunk and letting the branches wither away. To cut down the trunk, it is necessary to understand the nature of the biological phenomenon, which helps the tumor to avoid attack by the immune system, drugs and immunotherapy. The clue is that the pro-tumor mechanisms are united by one goal – to increase the resistance of the tumor cell to immune factors and drugs. A phenomenon that improves cell resistance is well known in biology – adaptation. If the immunity does not immediately destroy the tumor cell, the cell begins to adapt to it. Our hypothesis is that short range adaptation to immune factors plays a role in the formation of tumor tolerance for immunity and immunotherapy. This gives rise to the idea of reducing the survival of tumor cells by disrupting adaptation mechanisms. Indeed, “turning off” the immune system for a period of time before therapy and applying immunotherapy only to tumor cells that have lost their increased resistance could be a new approach to increase the effectiveness of immunotherapy.