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The Josep Carreras Leukaemia Research Institute has launched the REVEAL project, led by Dr. Natividad Alquézar-Artieda, with the aim of improving the effectiveness of immunotherapy in the treatment of leukaemia and other types of cancer. This project focuses on studying the transport of metabolites in the tumour microenvironment and its impact on immune cells, seeking a deeper understanding of the immune escape phenomenon.
Immunotherapy has made a huge difference in the fight against leukaemia. Today, doctors have a vast library of specific immune activating drugs, antibodies and even reprogrammed immune cells. Most of these treatments rely on the activity of the so-called effector T-cells, members of the immune system that can kill cancer cells when found.
However, tumours often modify its surroundings – the tumour microenvironment – to make it harsh for T-cells to be active, leading to tumour growth. Scientists call this “immune evasion” and understanding how they do it, and acting upon it, can increase the efficacy of immunotherapy beyond its current limits.
With this objective, the new REVEAL project, led by Dr. Natividad Alquézar-Artieda and supervised by Dr. Lucas Pontel, from the Cancer Metabolism Lab at the Josep Carreras Leukaemia Research Institute, will try to understand how tumours foster immune evasion from a novel perspective: metabolism.
Dr. Alquézar-Artieda, a Carreras Leaders postdoctoral researcher, is confident that REVEAL will “find ways to improve the efficacy of immunotherapy from a metabolic point of view, both from tumour cells and the microenvironment, a non-addressed issue so far”.
The REVEAL project
The research team hypothesized that the high metabolic rate of cancer cells could deplete key elements for T-cell activation – nutrients and signalling molecules – from the tumour microenvironment, resulting in low immune activity around it. The hypothesis is grounded by the fact that alterations in some transporters – proteins that move molecules back and forth from cells – are indeed related to poor prognosis in Acute Myeloid Leukaemia.
To test the hypothesis, Dr. Alquézar-Artieda and Dr. Pontel will use an in vitro culture model of an AML tumour with some crucial resident cells, including T-cells, and aspects of its microenvironment to test whether alterations in transporters known for being related to AML progression, can actually affect T-cell function and promote immune escape.
The first results will see the light by mid-2026 and, hopefully, will open new perspectives in the fight against leukaemia and, perhaps, other cancer types.
