An epigenetic test could one day help establish whether immunotherapy treatments for multiple myeloma will be effective for individual patients, Spanish researchers have reported.
A subgroup of patients has hypermethylation in the PVR gene, which the researchers found is a key regulator of the immune system, and makes myeloma cells more susceptible to some immunotherapies.
The findings, reported in the journal Leukemia, suggest a potential test to help establish the likely effectiveness of immunotherapy. It may also reveal a new target for therapies, the researchers say.
Hypermethylation of PVR would reduce the expression of the PVR gene. In an analysis of 776 patients from the CoMMpass dataset, the researchers found that patients with lower levels of PVR expression seemed to have longer overall survival than others. They speculated that the disease had additional vulnerability to the immune system because of the epigenetic change.
This was demonstrated in laboratory tests, using a cellular model of myeloma cells with the PVR gene eliminated, testing different forms of immunotherapy: antibodies, T-lymphocytes, CAR-T and CAR-NK cells. In all cases tested, the immune response was effective against the tumour cells, according to researchers at the Josep Carreras Leukaemia Research Institute, Barcelona, Spain.
Researcher Professor Manel Esteller said: “Our results demonstrate that in this malignant blood disease, inhibiting the PVR gene decisively increases the probability of success of immunotherapy. Now, then, it would be the turn of the pharmaceutical industry and clinical research to bring these results to the bedside of the patient.”
Source:
Martinez-Verbo L, Veselinova Y, Llinàs-Arias P, García-Prieto CA, Noguera-Castells A, Pato ML, Bueno-Costa A, Campillo-Marcos I, Villanueva L, Oliver-Caldes A, Cardus O, Salsench SV, García-Ortiz A, Valeri A, Rojas EA, Barrena N, Gutiérrez NC, Prósper F, Agirre X, Fernández de Larrea C, Martínez-López J, Ferrer G, Esteller M. (2024) “VR (CD155) Epigenetic Status Mediates Immunotherapy Response in Multiple Myeloma.” Leukemia, 24 September 2024, doi: 10.1038/s41375-024-02419-z
Link: https://www.nature.com/articles/s41375-024-02419-z
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