2018 Nobel Prize in Physiology or Medicine: Immunotherapy breakthrough
The 2018 Nobel Prize in Physiology or Medicine was awarded jointly to Dr. James Allison of the University of Texas, MD Anderson Cancer Center in Houston in the USA and Dr. Tasuku Honjo of Kyoto University in Japan. The widespread of cancer worldwide as a leading cause of death and its trend on the rise has undoubtedly become a matter of significant concern for the human population. Prevention strategies (based on more responsible conduct and the reduction of exposure to environmental carcinogens) only cover a small proportion of cancers, and survival rates are improving only for a limited number of cancer types. While drug and physical methods have been developed and engineered for combating cancer cells, these approaches are generally aggressive for the individual and short-lived, with the frequent possibility of treatment-resistance.
Importantly, Drs. Allison and Honjo have brought into the field of cancer treatment the use of the host’s own immune system by potentiating its activity and unleashing it’s killing capacity over transformed cells. Seldom commented, healthy individuals are constantly developing micro-tumors derived from naturally- or stimuli-transformed cells that undergo abnormal division. However, we are not aware of these microtumors, as immune cells within a healthy individual recognize these potentially malignant cells and destroy them before they expand into tumors or cancers, and acquire expanding (metastasis) or immune-evasion properties. Thus, the appearance of cancer in an individual may somewhat be understood as poor immune surveillance of these transformed cells in an otherwise healthy individual. Hence, stimulating the immune system to regain this capacity is an appealing rationale for combating cancer. Such an approach can be achieved by deactivating negative-regulatory mechanisms evolved by the immune system to control its reactivity power and is being colloquially referred to as “releasing the brakes” of the immune system.
But why would the immune system have brakes? Negative regulation of immune activation exists for many purposes, one of them being to avoid hyper-reactive immune responses that could be detrimental to the host, like those induced by some allergens reaching the respiratory tract. Another reason for this is to avoid auto-reactive responses against components that are natural constituents of healthy tissues and if not tolerated could lead to autoimmunity. Hence, releasing the brakes of the immune system may eventually lead to such processes at the macroscopic and/or microscopic level (symptomatic or asymptomatic), yet the benefit of an exacerbated immune response over cancer cells has shown to be more important than potential side effects that may arise in cancer patients.
This new cancer treatment, however, is open for improvements. For the moment, the breaks are released in such a way to broadly (non-specifically) activate the immune system, hoping that adequate immune components (mainly cytotoxic T cells) could be activated against the cancer cells. Thus, it is comprehensible that not all individuals respond favorably to this treatment. Indeed, effectiveness in eliminating cancer cells widely varies between cancers and individuals, ideally requiring personalized attention, which would increase the costs of treatment. Hence, defining those individuals that are most likely to respond to the therapy is an important research focus at this moment, with laboratories working on the identification of molecular markers that can predict treatment effectiveness. Further, combination treatment approaches that could increase the number of patients responding to immunotherapy is an intense area of current research, by combining for example chemotherapy, targeted therapy or other forms of immunotherapy.
In parallel to the importance in improving the scientific understanding of cancer development to devise better approaches of treatment, a critical aspect that needs to be seriously considered and addressed is to put in place economic models that would ensure that effective immunotherapies are accessible to patients globally. At present, the cost of immunotherapies is gradually increasing with price tags usually above the $100,000 USD range per patient per year (Nature 555, S26-S29 (2018), doi: 10.1038/d41586-018-02483-3). As reported by the International Agency for Research into Cancer (IARC; doi: 10.3322/caac.21492), the incidence of cancer will continue to rise in the coming years with higher rates in the developing countries. This would inevitably increase the disparity to cancer treatment and requires urgent intervention.
Dr. Pablo González is an Assistant Professor and Associate Investigator at the Millennium Institute on Immunology and Immunotherapy at the Department of Molecular Genetics and Microbiology at the Faculty of Biological Sciences at the Pontificia Universidad Católica de Chile. He is a Young TWAS affiliate since 2017 and TYAN (TWAS Young Affiliate Network) member.
Dr. Sok Ching Cheong is a Senior Group Leader at Cancer Research Malaysia. She is a TYAN (TWAS Young Affiliate Network) member and Honorary Member of the Young Scientists Network, Academy of Sciences Malaysia.