Mats Hellström – Markers and mechanisms in lymphoma immunotherapyMarkörer och mekanismer vid immunterapi av lymfom

My research has two main directions. The first is to study how the immune system reacts to cancer. More specifically, we are interested in how the dendritic cells are controlling the immune response. The second is to identify new biomarkers to provide better diagnosis, prognosis and treatment of lymphoma patients.

Cancer develops due to damage to the genetic material, DNA, which leads to loss of growth control and formation cancer cells. Cancer deviates from normal cells and can under certain circumstances be recognised by our immune system. In order for cancer cells to be recognised and attacked by the immune system, several tightly intertwined events are required that must take place in the immune system. This is usually described as ‘the cancer immunity cycle’, initially described by Chen and Mellman 2013.

Cancer immunotherapy

In recent years, immunotherapy has been established as an effective and safe cancer treatment. In particular, checkpoint inhibitors, which target inhibitory signals in the tumour’s microenvironment, have been successfully implemented in cancer treatment.

However, not all patients benefit from the treatment with immune checkpoint blockade. The complex interaction between the cancer cells and the tumour’s microenvironment means that the immune cells are suppressed to varying degrees in all types of cancer. Intensive research is underway to try to understand why checkpoint inhibitor treatment fails in some patients.

Lymphomas in different subgroups

Lymphoma is a group of cancers that originate from lymphocytes, a type of white blood cell. It usually originates from lymphocytes called B cells and is most often localised to lymph nodes in the body. Lymphoma can be divided into many subgroups. The most common aggressive lymphoma is diffuse large B-cell lymphoma and the most common indolent lymphoma is follicular lymphoma. Depending on the lymphoma type, treatment and prognosis are remarkably different as the disease can vary from very aggressive to indolent.

Immunotherapy against lymphoma

Lymphoma has long been treated with a type of immunotherapy based on antibodies directed against B cells. In recent years, ‘chimeric antigen receptor’ (CAR) T cells have been established as a treatment against lymphoma. The patient's own T cells are genetically modified outside the body and then given back to the patient to fight the lymphoma (see figure 1). Additional immunotherapies in the form of bi-specific antibodies that recruit and activate T cells are in rapid development, with the first approved products recently on the market.

Our research on cancer immune response and improved diagnosis, prognosis and treatment

Despite great success in the development of immunotherapy, there are patients who do not respond to treatment. We also know substantially less about how immunotherapy works in patients with brain tumours.

The current projects in the lab aim to address the following questions:

How do dendritic cells shape the immune response against cancer in or outside the central nervous system?
Can plasma proteomics (analysis of thousands of proteins in blood plasma) differentiate between different types of cancer and lymphoma and help us predict prognosis or response to treatment?

We work widely with different techniques and methods that range from basic cell biology studies with multi-colour flow cytometry to ‘-omics’ analyses of patient samples.