T-Cell Acute Lymphoblastic Leukemia (ALL) - a very aggressive and rapidly progressing leukaemia affecting T lymphocytes - is treated with chemotherapy, which is usually effective. However, 10 per cent of paediatric and 60 per cent of adult patients experience tumour progression even after chemo.

A new study, coordinated by Isabella Screpanti and Antonio Francesco Campese of the Department of Molecular Medicine of Sapienza University, has identified one of the mechanisms involved in most cases of T-ALL.

The research, published in the journal Frontiers in Immunology, is a collaboration between Molecular Medicine and Experimental Medicine departments at Sapienza University of Rome and the Italian Institute of Technology. The Airc Foundation also contributed.

The researchers worked with laboratory mice genetically modified to have alterations in the Notch pathway - a biochemical signalling pathway that regulates the proliferation and differentiation processes of different cell types, including T lymphocytes - responsible for the development of certain forms of T-ALL.

Thus, specific cells of the immune system involved in tumour recurrence, namely myeloid suppressor cells, have been identified. When in large numbers, these cells, which are usually responsible for blocking the immune response to prevent it from becoming excessive, also reduce the immune response against cancer cells.

T lymphocytes, which in the case of T-ALL are also tumour cells, are among the natural targets of myeloid suppressor cells and, therefore, were expected to inhibit tumour proliferation. However, this is not the case, because the leukemic cells are able to turn the action of the myeloid suppressor cells in their favour.

The results of this research show that interleukin-6 (IL-6), a protein molecule produced by tumour cells themselves, promotes the development of suppressor cells. Indeed, experiments confirm that administration of IL-6 inhibitors limits the expansion of these cells, both in animals and in cultured human leukaemia cells.

"The study", says Isabella Screpanti and Antonio Francesco Campese, "could make a crucial contribution to the development of new therapies based on the use of IL-6 inhibitors for patients with LLA-T who do not respond to other treatments in use".

References:

Notch-Signaling Deregulation Induces Myeloid-Derived Suppressor Cells in T-Cell Acute Lymphoblastic Leukemia - Paola Grazioli, Andrea Orlando, Nike Giordano, Claudia Noce, Giovanna Peruzzi, Behnaz Abdollahzadeh, Isabella Screpanti, Antonio Francesco Campese - Frontiers in Immunology (2022) https://doi.org/10.3389/fimmu.2022.809261

Further Information

Isabella Screpanti
Department of Molecular Medicine
isabella.screpanti@uniroma1.it

Antonio Francesco Campese
Department of Molecular Medicine
antonello.campese@uniroma1.it