A research team from the University of Helsinki has demonstrated that the immune system attacks itself in a rare type of blood cancer, large granular lymphocyte leukaemia.
According to the latest international assessment, one in two people will develop cancer at some point in their life. Blood cancers and other previously rare cancer types, such as large granular lymphocyte leukaemia, are also becoming increasingly common in the population. Thus, the study of rare cancers is important not only for improving the treatment of patients suffering from them but also because it can teach us about what makes other cancers vulnerable.
What is large granular lymphocyte leukaemia?
Large granular lymphocyte leukaemia is a rare type of cancer in which the body’s immune cells (T cells) form the cancer cells. This cancer is rarely fatal, but it causes several chronic symptoms, including an increased infection risk, anaemia, and joint pain.
The symptoms are believed to be caused by the large granular lymphocyte leukaemia cancer cells attacking the body’s own tissues – this cancer resembles autoimmune diseases. Current therapies are usually not curative, and patients’ symptoms return quickly.
“Our research group demonstrated 10 years ago that large granular lymphocyte leukaemia cancer cells typically have a mutation in the STAT3 gene, a finding that is now used to diagnose this disease worldwide,” explained Professor of Translational Haematology Satu Mustjoki from the University of Helsinki.
“Researchers have previously analysed primarily large granular lymphocyte leukaemia cancer cells, but we wondered whether other cells of the patient’s immune system could also have a role in this disease,” added Doctoral Researcher Jani Huuhtanen, LicMed, from the University of Helsinki and Aalto University.
How did scientists examine these cells?
Researchers noted that separating the normal cells associated with the immune system from the blood cancer cells by traditional methods proved to be extremely difficult. This is because, in this type of leukaemia, cancer cells bear a very close resemblance to normal T cells found in blood.
Therefore, novel single-cell techniques have enabled a breakthrough that has made it possible for scientists to examine individual cells one at a time. With these techniques, the researchers were able, for the first time, to separate cancer cells from normal T cells and compare them with each other.
“Single-cell techniques open up entirely new avenues for research,” said Tiina Kelkka, Docent of Immunology from the University of Helsinki.
“But we still needed a large patient cohort, which is hard to gather in rare diseases. Thanks to our research group’s international collaboration network, we were able to compile a dataset of almost 200 large granular lymphocyte leukaemia patients’ samples from Finland, Germany, Italy, the USA and Japan.”
What was revealed from this examination?
This extensive dataset proved the group’s hypothesis to be correct: in large granular lymphocyte leukaemia, the whole immune system, not just the large granular lymphocyte cancer cells, is clearly distinct from other cancers.
“The immune system in these patients is overactivated and keeps giving the tumour cells cues to keep growing as well as provides them with a favourable environment,” noted Dipabarna Bhattacharya, Doctoral Researcher from the University of Helsinki.
Therefore, these findings suggest that current therapies for large granular lymphocyte leukaemia should target the whole immune system, not only the cancer cells, to increase the quality of life of patients.
“We believe that similar findings will be made in other cancers. In fact, our goal is to use the same techniques to decipher the role of the immune system in other cancers too,” concluded Jani Huuhtanen.