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Content archived on 2024-05-29

Anti-tumour CD8 immunity influenced by epigenetic alterations

Final Activity Report Summary - IMMUNOEPIGENETICS (Anti-tumour CD8 immunity influenced by epigenetic alterations)

Cancer Immunoepigenetics refers to an innovative approach attempting to understand the underlying biological framework of the anti-cancer immune response. It deals with epigenetic alterations of immune or other genes in immune cells that can affect their function. The postulate underlying this project, states that the spreading of epigenetic alterations within cancerous cells is also affecting the expression of immune genes, and/or other genes of immune cells. This in turn, is then altering the ability of the immune system to combat tumours - a key element in carcinogenesis. It is therefore quite possible that any epigenetic aberration of immune genes will affect anti-tumour immune responses. Moreover, if this aberration occurs on the CD8 T cell then the ability of the immune system to combat tumours is severely compromised.

This project aimed in clarifying whether epigenetic alterations of immune genes or tumour-related genes induced by epigenetic drugs, affect the CD8 effector cytolytic T cell response in lung cancer. Both unmanipulated CD4 and CD8 T cells as well as tumour specific CD8 T cell clones were cultured in the presence of epigenetic drugs (ED). All cells were assessed with respect to their proliferative and functional capacity as a result of the ED presence. Our results indicate that culturing T cells in the presence of ED, reduces their ability to recognise and destroy tumour cells. Moreover, these cells appear to acquire an immunomodulatory phenotype.

These findings are quite intriguing since for the first time, a completely different and scientifically justified approach into the origins of ineffective CD8 mediated anti-cancer immunity is observed. Exploiting further the immunomodulatory effect of these drugs on the cytolytic T cell, could provide new and improved approaches towards clinically effective cancer immunotherapy.