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El inmunólogo Tak Mak, en el Centro Nacional de Investigaciones Oncológicas (CNIO). /A. Tabernero. CNIO
“Medical scientists have two lives, and the second one begins when they realise immunology is the orchestra of all life symphonies”
“Some people think they know why immunotherapy works, why T cells kill the tumour, but we do not know. We need to find out”.
“By this time of my career, I am only interested in making sure that the few ideas that I have will be exploited by yet another generations of trainees and collaborators”
Tak W. Mak (Hong Kong, 1946) is the author of some of the major findings of recent decades on the causes and treatment of cancer. His discovery of the T-cell receptor –a mechanism by which the body identify invaders— made cancer immunotherapy possible. He also paved the way to the development of new cancer drugs against specific mutations. He recently visited the Spanish National Cancer Research Center (CNIO) at the invitation of Nabil Djouder, head of the Growth Factors, Nutrients and Cancer Group.
He insists that current knowledge about immunology is still “superficial”, and “society should spend more time educating the next generation of immunologist”.
You are an immunologist, but your contributions span different areas. Your conference at CNIO is about metabolism. What is the common thread in your career?
Metabolism, immunology, tumour micro-environment… they are all connected at the level of physiology. In 1966 cancer was thought to be a metabolic disease. A group of Nobel laureates, including Otto Warburg, concluded back then that cancer is neither caused by virus nor by genes, but by the replacement of respiration by the fermentation of sugar. But cancer is indeed caused by genes because of mutations, and each of these mutations change metabolism in order to adapt. Mutations, epigenetic or somatic, change the cell that is being mutated, and change the tumour micro-environment as well.
And virus induce cancer, too.
Yes, virus like the papilloma virus, the Epstein Barr virus, the hepatitis B and C virus… they create an inflammatory environment whereby cancer cells can increase their mutations. But that, in turn, have to have the metabolism of your cells to adapt, otherwise the pre-cancer cell would die, and there would be no cancer.
The fact that metabolism, immunology and tumour microenvironment are interconnected, is the reason why cancer is so difficult to treat?
Everything is highly interconnected, and that is the reason we need to have a very broad view of the development of cancer to either prevent it, or treat it.
Immunotherapy is said to be the great revolution in cancer treatment. Is this your view?
Immunotherapy using immune-checkpoint modulators, the equivalent to taking off the breaks of the T cells [to make them kill cancer cells more effectively], is one of the pillars of cancer treatment. Today some people think they know why it works, why T cells are killing the tumour, but I have to say they are misled, because we do not know. We need to find out.
What about immunotherapy with CAR-T cells, in which T cells from the patient are modified in the lab to make them recognize and kill cancer cells?
CAR-T has spectacular results, in refractory/relapse leukemias and lymphomas. It’s like in the Jason Bourne movies. Bourne is a genius, he can jump into enemy territory, find its way into the bad guy, beat it and find its way back. That is CAR-T. However, there are very limited number of cell-surface molecules that T cells can recognise as cancer. Companies and scientists are having trouble finding more, to make the next generation of CAR-T.
Will researchers succeed in improving the efficacy of immunotherapy? Are you optimistic?
I am Chinese, I can quote Confucius. Confucius said: “We all have two lives, and the second one begins when we realise, we only have one”. It is a very deep thought, especially for someone of my age. Medical scientists –in the field of cancer, or immune disease, or neurodegeneration, or cardiac diseases…– have two lives, and the second one begins when they realise immunology is the orchestra of all life symphonies. So, I totally believe the immune system, and its knowledge, will be an essential part of not only cancer, but of many other diseases that humankind is going to have to face in the next decades.
Other pioneers of immunotherapy have received the Nobel prize. Should you have also?
I am not doing science for recognition. By this time of my career I am only interested in making sure that the few ideas that I have will be exploited but yet another generations of trainees and collaborators. I want to be recognised and remembered as the person who planted more seeds, nurtured them, and made sure there would be more beautiful flowers to blossom.
In which field of cancer research would you spend more resources?
Everywhere I go I see a critical shortage of new scientists going into immunology. I think society should spend more time educating the next generation of immunologists. Immunology needs to be studied more deeply and systematically. We cannot afford to just superficially address immunological impacts on physiology. Immunology is so complicated that it can easily be simplified to the point where it could be misleading.