Cancer Treatment: not to destroy, but to age the tumor cells
The immune system includes a cellular aging program in cancer cells
LifeSciencesToday based on the materials of Universitatsklinikum Tubingen: Meilenstein in der Krebsforschung – Immunsystem treibt Krebs in DauerschlafThe group of Professor Martin Rocken from the University Clinic of Tubingen has shown for the first time that the immune system is able to transfer cancer cells and tumors to a state of permanent rest.
The suppression of cell growth due to this ability of the immune system makes it possible to control the tumor without destroying cells. A state of permanent rest – known as cellular senescence, or senescence - can persist throughout the life of an organism. Thus, immunotherapy can prevent the development of a tumor without destroying its cells.
Professor Reken, director of the Dermatology Department at the University Clinic of Tubingen, describes the current state of cancer therapy as follows: "About 50 years ago, former President of the United States of America Richard Nixon announced the beginning of the "war on cancer". In order to defeat this devastating disease in a relatively short time, large financial and logistical resources were involved. During this time, scientists and clinicians have learned to use chemotherapy and natural killer cells to directly attack cancer cells and destroy malignant tumors, including their environment. This has led to several very important and even brilliant achievements in understanding the development of tumors and improving the diagnosis of cancer. Moreover, thanks to innovative methods – surgical technologies, radiation, chemo- and immunotherapy – notable successes have been achieved in the treatment of certain types of cancer. However, the main goal, that is, a decisive victory over cancer, has remained unattainable."
Recently, Professor Reken continues, doubts have been expressed about the viability of the strategy of the "war on cancer", focused solely on the destruction of cancer cells.
Two well–known signaling molecules associated with cancer therapy and the immunology of infectious diseases - interferons and tumor necrosis factor - have again become the focus of medical attention.
Attempts to use these molecules to destroy tumor cells and blood vessels feeding them have been made repeatedly, but unsuccessfully by many scientists and clinicians, including researchers from Tubingen. However, Professor Requen was able to establish that the growth of tumors in vivo without any signs of destruction of cells or tissues is stopped by a certain combination of these two signaling molecules.
In animal experiments (this was first shown in pancreatic islet cell cancer), researchers have proven that the effectiveness of immunotherapy-induced cellular aging is much higher than the effectiveness of any therapy focused on "cancer destruction". The inclusion of a cellular aging program can unexpectedly suppress tumor development for a long time. Moreover, isolated "dormant" tumor cells of animals transplanted to healthy immunodeficient mice did not begin to grow, but remained – without treatment – at rest. They no longer behaved like uncontrollably growing tumors.
Former melanoma cells (shown in red), transferred by the immune system to the state of,
characterized by the cessation of division, that is, senescence.
(Photo: Universitaet Tubingen)
It is important to note that, according to Professor Requin, the immune response translates into the state of aging of tumor cells and human origin. The human body, apparently, protects itself from cancer by including a senescence program in tumor cells and thereby suppressing the growth of a malignant neoplasm.
But the most important thing is that the combined action of two signaling molecules, interferon and tumor necrosis factor, stops the growth of human tumors. The activation of the cellular aging program during the natural immune response occurs even in regressing malignant tumors of patients.
The fact that cancer cells can, in principle, be transferred to a dormant state, that is, to a state of cellular aging, was first shown seven years ago. Now these theoretical concepts have been successfully translated into a therapeutic approach – an immunotherapy protocol.
The new approach will allow doctors to get closer to their goal of prolonging the life of patients using methods that practically do not cause adverse side effects.
"Probably, cancer can and should be defeated not only by means of destruction," sums up Professor Reken. – The alternative to this should be the goal of restoring the body's immune control over malignant tumors."
Article by Braumulle et al. T-helper-1-cell cytokines drive cancer into senescence T-helper-1-cell cytokines drive cancer into senescence is published in Nature.
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