Immunostaining of H4K20me3 (crimson). Credit score: IRB Barcelona
Most cancers therapies don’t all the time reach eliminating tumor cells. A few of these cells enter a state of senescence—a latent, non-dividing state that’s typically irreversible. Others, nonetheless, enter a state generally known as “persistence,” the place dormancy is momentary and reversible. This state permits the cells to start rising once more after the therapy has ended, resulting in most cancers recurrence.
A workforce led by Dr. Manuel Serrano at IRB Barcelona has found a key technique by means of which these persister cells evade the immune response and resist most cancers therapies. Particularly, the examine reveals that persister cells block the genes liable for irritation by means of an epigenetic mechanism that acts as a “molecular lock,” stopping these genes from turning into activated and alerting the immune system.
This lock stops the immune system from detecting and eliminating these cells, permitting them to withstand therapy. This contrasts with senescent cells, that are extremely inflammatory and use totally different mechanisms to evade the immune response.
“This epigenetic silencing is a weakness of persister cells and could be leveraged to design new therapeutic approaches,” says Dr. Serrano, head of the examine and presently working at Altos Labs (Cambridge, UK).
The examine, first-authored by Dr. Valentina Ramponi, has been revealed within the journal Most cancers Analysis.
A promising therapeutic method
Along with figuring out this mechanism, the examine exhibits that inhibiting the epigenetic mechanism may unlock inflammatory genes and compromise the viability of persister cells, thus paving the way in which for the event of recent therapies. This speculation was confirmed by means of experiments with particular inhibitors, opening the door to the design of focused therapies.
Graphical Summary. Credit score: Most cancers Analysis (2024). DOI: 10.1158/0008-5472.CAN-24-0529
“The goal is to be able to develop drugs that selectively target persister cells and strengthen the effect of conventional treatments,” concludes Dr. Ramponi, now a postdoctoral researcher on the AIRC Institute of Molecular Oncology.
This discovery marks a step ahead within the battle towards resistance to most cancers therapy. By focusing on persister cells, the probability of relapse could possibly be diminished, thus bettering affected person prognosis.
The examine was completed in collaboration with the Rovira i Virgili College, the Queen Mary College of London, the CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), the AIRC Institute of Molecular Oncology, and Altos Labs’ Cambridge Institute of Science.
Extra info:
Valentina Ramponi et al, H4K20me3-Mediated Repression of Inflammatory Genes Is a Attribute and Targetable Vulnerability of Persister Most cancers Cells, Most cancers Analysis (2024). DOI: 10.1158/0008-5472.CAN-24-0529
Offered by
Institute for Analysis in Biomedicine (IRB Barcelona)
Quotation:
New mechanism that shields persister tumor cells from immune system recognized (2025, January 15)
retrieved 16 January 2025
from https://medicalxpress.com/information/2025-01-mechanism-shields-persister-tumor-cells.html
This doc is topic to copyright. Aside from any honest dealing for the aim of personal examine or analysis, no
half could also be reproduced with out the written permission. The content material is offered for info functions solely.
