A team of scientists, coordinated by the University of Milan, has identified for the first time a mechanism involving molecules that were considered useless until a few years ago. Instead, they are essential to activate the correct function of our immune system against tumors
They are called LINE1 molecules and were considered junk DNA, because they were repeated many times without a known function, while they play a crucial role: they are in fact capable of activate the immune system response against the tumor and help him recognize and eliminate cancerous cells. The researchers of the University of Milan in a study published in Nature Genetics
and then also accompanied by an editorial comment in the same scientific journal.
The news
The research was coordinated by Beatrice Bodegaprofessor of Molecular Biology, e Sergio Abrignani, lecturer in General Pathology, both of the University of Milan and the Romeo and Enrica Invernizzi National Institute of Molecular Genetics, and was created in collaboration with the IRCCS Istituto Clinico Humanitas and the Humanitas University of Milan, the CheckmAb spin -off of the State of Milan, the Great Metropolitan Niguarda Hospital of Milan, the Polyclinic of Milan, the San Giuseppe MultiMedica IRCCS hospital in Milan. The great novelty of our work is precisely that of being able for the first time to attribute an important function to certain sequences of human DNA (the LINE1 molecules, in fact), for years considered unimportant and which we now know to be essential for the activation and function of immune cells, in particular T lymphocytesand they can become a pharmacological target in innovative immunotherapy strategies emphasizes Sergio Abrignani.
When the immune system is blocked
These DNA sequences are transformed into Rna in some cells of the immune system, the quiescent T lymphocytes, where they act as a “molecular brake” that prevents the lymphocytes from carrying out their defense function – explains Beatrice Bodega -. Our work describes how T lymphocytes, when activated, get rid of this “molecular brake“With a sophisticated mechanism (completely new and never observed before) that allows lymphocytes to perform their functions, including that of eliminate cells that are recognized as foreign. The study was conducted on cells deriving from healthy donors and on tumor tissues isolated from neoplastic patients. The point of great interest described by the study is that the same molecular brakes are present in the T lymphocytes that surround the tumor cells, without being able to eliminate them because they are suppressed by the environment present in the neoplastic tissue.
The next step: developing new therapies
The Milanese team of researchers has shown that it is precisely the abnormal and unexpected presence of these “molecular brakes” in intra-tumor lymphocytes that suppresses their immune activity against cancer. And, very relevantly, we have also shown that if we remove these suppressor molecules with experimental therapeutic approaches, T lymphocytes reactivate and are able to kill cancer cells adds Bodega. We believe we have identified a potential new therapeutic target to be combined with today’s immunotherapies with antibodies against checkpoint inhibitors – concludes Abrignani -. The future goal is to create a startup that can develop new therapies which, by turning off LINE1 RNA in intra-tumor T lymphocytes, can awaken the silent immune system in the intra-tumor microenvironmentso that the T lymphocytes can again recognize and destroy the neoplastic cells.
January 31, 2022 (change January 31, 2022 | 18:49)
© REPRODUCTION RESERVED
#Discovery #fight #cancer #junk #DNA