Leiden University: Thorbald van Hall delivers inaugural lecture on training the immune system to counterattack escaping tumors

Despite representing a major problem in modern society, cancer is not a recent disease. First described in ancient written sources by Egyptian physicians, and more recently confirmed in human mummies, tumor growth has manifested itself throughout human history. Unprecedented understanding and systematic treatment of the disease was then made possible with the emergence of modern medicine and technological advances of the 20th century, particularly in molecular cell biology and genetics. Nevertheless, the relationship between one’s immune system in preventing and counterattacking tumors became apparent only in the last 20 years.

Revolutionizing treatment
‘These developments have led us to different types of immunotherapies, which revolutionized the approach to treatment of a dozen tumor types, including lung, kidney, certain breast and colon cancers’, says Thorbald van Hall, Professor of Experimental Tumor Immunology at the Department of Medical Oncology at the LUMC. There are currently seven immunotherapy drugs available that work in similar manners. To improve these treatments, Van Hall and his research group are focused on expanding the field by exploiting new therapeutic targets: ‘After many years of fundamental research, we have demonstrated a novel way to help the immune system recognize ‘disguised’ cancer cells. This is quite exciting, as soon we will be the first to test this knowledge in clinical trials’.

Immunotherapy training
In contrast to conventional cancer treatments – which directly target tumor cells – the main goal of immunotherapy is to ignite an immune response instead that attacks the cancer. Van Hall explains: ‘the treatment works by teaching the immune system to become better at catching cancerous cells’. This is important because tumors will often adapt to escape from being controlled. ‘Eventually, cancers may become resistant and recurring. But since the immune system has memory, through previous training and our novel therapy interventions, it can learn to identify those modifications and prevent future escapes in the long run’.

Cancerous outlaws and the immune police
One of Van Hall’s major research interests lies in understanding the escape mechanisms tumors adopt, also against treatments. According to the Professor: ‘simply put, cancer is a proliferation of tissue that is not controlled by the body because it bypasses the regular checks that normal cell growth is subject to; just like outlaws. Similar to the police, the immune system represents the enforcers of law and order, but its agents may not always be fully prepared to capture certain bad guys. As an intervention, immunotherapy can be used’.

However, if there is one thing the history of villains has taught us is that they are always plotting their next comeback. ‘Tumors will scheme new ways to trick the immunotherapy-trained system too. My fundamental and pre-clinical research focuses on unraveling their breakout plans, so that we can counterattack once more with alternative strategies that will render these cancers vulnerable to the immune system’, Van Hall notes.

Global burden of cancer
In the Netherlands, approximately 115,000 people are diagnosed with cancer each year, of which about 65% get successfully treated. 45,000 cases lead to death. This represents a major social and economic burden that requires a comprehensive response, including prevention, early detection and treatment. Van Hall concludes: ‘As long as the disease exists, people will try to find a treatment for it. From natural products used in the past; to the biological molecules of the present, exploring innovative therapies will remain an area of focus for research. Now, we are slowly beginning to understand at the molecular level what causes cancer and where things go wrong. My ambition, therefore, is not only to gain more insight about the interplay between the immune system and tumors, but also in the response or resistance to therapy and disease occurrence. In this way, we will enable an increasing number of cancer patients to be effectively treated’.