04 May 2022

Researchers looking at large granular lymphocyte leukaemia have found a previously unknown role for the immune system.

T-cell Large Granular Lymphocytic Leukaemia (T-LGLL) is a rare condition involving the build-up of abnormal T cells in the blood, bone marrow, and spleen. It is normally manageable with low-dose immunosuppressants. Mutations in the STAT3 gene are present in 40% to 50% of patients, who tend to have greater symptoms.

It has been suggested that a chronic T cell response to antigens drives the condition, though altered B-cell activities, and elevated cytokines and interleukins, also point towards the involvement of non-leukaemia immune cells in the disease.

Researchers led by a team from University of Helsinki, Finland, jointly led by Professor Satu Mustjoki and Dr Tiina Kelkka, argue that “a holistic understanding of the total immune repertoire behind T-LGLL is an unmet need”.

The team used RNA and T cell gene sequencing to identify where the condition stands in “the intersection of cancer, autoimmune disorders, and chronic inflammation”.

Their work showed that irrespective of STAT3 mutation status, these leukaemia T cells are in more active communication with non-leukaemic immune cells than previously realised.

Results suggested that “future therapies should be geared toward attenuating the entire immune system and not the T-LGLL clone alone,” they write.

Jani Huuhtanen, co-first author with Dipabarna Bhattacharya, said: “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.

“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.”

Source: Huuhtanen J, Bhattacharya D, Lönnberg T, Kankainen M, Kerr C, Theodoropoulos J, Rajala H, Gurnari C, Kasanen T, Braun T, Teramo A, Zambello R, Herling M, Ishida F, Kawakami T, Salmi M, Loughran T, Maciejewski JP, Lähdesmäki H, Kelkka T, Mustjoki S.  (2022) “Single-cell characterization of leukemic and non-leukemic immune repertoires in CD8+ T-cell large granular lymphocytic leukemia.” Nature Communications, doi: 10.1038/s41467-022-29173-z

Link: https://www.nature.com/articles/s41467-022-29173-z

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