IMMUNOEPIGENETICS · Anti-tumour CD8 immunity influenced by epigenetic alterations
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-02-01 → 2009-01-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- EIF
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Results in brief
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.
Data: CORDIS, © European Union
Project objective
Cancer is a systemic disease characterized by a plethora of epigenetic alterations with extensive disturbances of DNA-methylation that play a crucial and nodal role in carcinogenesis. However, the question that arises is whether similar epigenetic alterations can also take place in genes of immune cells and interfere with the anti-tumour immune response.The hypothesis underlying this proposal postulates that spreading" of epigenetic alterations is taking place in cancer affecting the expression of immune genes, and/or other genes of immune cells which, in turn, alter the ability of the immune system to combat tumours. This study approaches the epigenetics of the immune system of cancer patients through their functional consequences on the effector CD8 T cell anti-tumour immune response. Moreover, since one of the tools used for these studies is epigenetic drugs, this project offers a unique methodological approach for screening the efficacy of these on the immune functions, prior to therapeutic applications.The proposal will drive further our understanding of the tumour-immune system relation, and benefit cancer immunotherapeutics. This innovative approach for cancer immunology creates a fertile common ground upon which the most forefront field of genetics along with cellular immunology will work towards the better understanding of carcinogenetic mechanisms and the improvement of cancer immunotherapy."
Original text from CORDIS.
Participants
- UNIVERSITY OF THESSALY · VOLOSCoordinatorCity levelGreece
Links
Data: CORDIS, © European Union