Glioblastoma is the most aggressive form of brain tumour in adults and the therapeutic options available today are very limited. The severe hypoxia (lack of oxygen) and immunosuppression that characterise the microenvironment of this tumour make even the latest immunotherapy strategies ineffective.

A new study published in the journal Immunity, the result of a collaboration between researchers from the Moffitt Cancer Center in Tampa, Florida, coordinated by Filippo Veglia, and researchers from the Department of Experimental Medicine at Sapienza University of Rome, coordinated by Aurelia Rughetti, identified a subpopulation of immune cells, the macrophages, characterised by high levels of the glucose receptor (GLUT1) that show a marked immunosuppressive capacity, capable of inhibiting the immune response and favouring the progression of glioblastoma.

"Our work", says Aurelia Rughetti of Sapienza University of Rome, "showed that the immunosuppressive activity of GLUT1+ macrophages present in the tumour is regulated at the epigenetic level by lactylation, which involves the addition of lactate on the lysine residues of histones. This recently described molecular mechanism appears to be responsible for the metabolic reprogramming of the GLUT1+ macrophage population, which is thus able to suppress anti-tumour T lymphocytes".

The characterisation of this immunosuppressive cell population and the identification of the molecular mechanism by which macrophages are reprogrammed in the tumour represent potential new targets for the development of new therapeutic approaches with which to remove the blockade of immunosuppression and thus enhance the effectiveness of immunological therapies.

The project involved PhD students Alessio Ugolini, Fabio Scirocchi and Angelica Pace from the Network Oncology and Precision Medicine PhD programme, coordinated by Aurelia Rughetti and Marianna Nuti from the Department of Experimental Medicine, and clinicians Luca D'Angelo and Antonio Santoro from the UOC of Neurosurgery of the Policlinico Umberto I General Hospital.

References:

Glucose-driven histone lactylation promotes the immunosuppressive activity of monocyte-derived macrophages in glioblastoma - De Leo A, Ugolini A, Yu X, Scirocchi F, Scocozza D, Peixoto B, Pace A, D'Angelo L, Liu JKC, Etame AB, Rughetti A, Nuti M, Santoro A, Vogelbaum MA, Conejo-Garcia JR, Rodriguez PC, Veglia F. - Immunity 2024 DOI 10.1016/j.immuni.2024.04.006.

Further Information

Aurelia Rughetti
Department of Experimental Medicine
aurelia.rughetti@uniroma1.it