Immunotherapy is a powerful way to treat cancer patients but up till now, it was hard to predict why some patients or cancer types do not benefit from this treatment. By investigating the immunological environment of different cancer types and comparing it with patient data, researchers could identify crucial T cell markers which predict a patient's or cancer type's response to immunotherapy. For some cancers, immunotherapy can be safely integrated into the standard treatment but for others, further research is needed to either alter the immunological environment with cancer vaccines or to develop a new type of immunotherapies that target the tumour in another manner.
Cancer is one of the most common diseases and a leading cause of death worldwide. Although new and efficient therapies are being developed, it is important to know from which treatment a patient will benefit the most. By using biomarkers, oncologists can better understand the specifics of each patient and adapt the treatment to their personal profile. A group of international researchers, under the leadership of Professor Abhishek D. Garg from KU Leuven, studied the immunological environment of five different tumor types, defining biomarkers that predict the patient's response to immunotherapy.
This study is already a huge step forward in defining the right biomarkers to predict a patient's or cancer type's response to current immunotherapy.
Professor Abhishek D. Garg
Is immunotherapy for everyone?
Immunotherapy was recently established as a very powerful way to treat cancer patients. The huge advantage compared to already existing treatments is that it uses the patient's own immune system to attack cancer cells. In this way, it can not only destroy the cancer cells anywhere in the body but also help our immune system to build up a memory against cancer cells thereby providing a long-term curative benefit. Thus, immunotherapy is a good treatment option for many cancer patients. However, not every cancer type is sensitive to this treatment, and until now, we didn't fully understand why.
"It can be dangerous to randomly treat cancer patients with one-size-fits-all immunotherapy", says Professor Abhishek Garg from the Department of Cellular and Molecular Medicine. "Pre-selection of patients is necessary to prevent severe side-effects from wrongly administered immunotherapy and/or, unnecessary delay in providing other more accurate therapeutic interventions. Therefore, we need biomarkers to predict which kind of immunotherapy is a suitable treatment for a particular patient or cancer type."
The researchers investigated the immunological environment of different tumors and distinguished two different classes. In one class (consisting of melanoma, bladder cancer, and lung cancer), the immunogenic environment displayed typical signs of being supportive for immunotherapy, and accordingly, most of these patients showed a positive response to this treatment. On the contrary, the second class [consisting of glioblastoma (brain cancer) and ovarian cancer] showed an immunotherapy non-supportive environment with signs of hostility toward anti-cancer immune structures.
By harmonizing the environmental features of this second class of tumors with patient data and response to immunotherapy, this study could identify markers of T cell 'fitness' - a specific type of immune cell that is critical for immunotherapy response - that clarified the failure of immunotherapy in these particular patients. Especially in glioblastoma, the researchers identified that T cells were in such a bad state that they were not likely to respond to current antibody-based immunotherapies thus demanding a more radical immunotherapy approach, compared to what is sufficient for melanoma or lung cancer.
Implementation as standard treatment
Currently, antibody-based immunotherapy is part of the standard treatment for, melanoma, lung cancer, and bladder cancer, amongst others. This research showed that other cancer types like ovarian cancer and glioblastoma need a different approach and further research to reveal new immunotherapeutic targets, as their only alternative is invasive surgery combined with chemotherapy and radiation. Another solution might be the use of anticancer vaccines that can improve the fitness of T cells in these hostile tumor environments and perhaps make them sensitive to antibody-based immunotherapy.
"Further research is needed to better understand how an anticancer vaccine can be used in these patients and how to combine it with current therapies like chemotherapy or radiation and antibody-based immunotherapy", concludes Professor Garg. "This study is already a huge step forward in defining the right biomarkers to predict a patient's or cancer type's response to current immunotherapy. We are now working closely with oncologists in UZ Leuven and Germany to start new clinical trials to upscale this practice and implement it in the daily practice of a hospital. This is urgently needed due to the extreme morbidity combined with few therapeutic options available against aggressive diseases like glioblastoma."
