"Immune Risk Profile" in cancer and ageing?
Professor Graham Pawelec
Head of the Tübingen Tumour Immunology and Ageing Group (TATI)
University of Tübingen
Germany
Time: 2010, monday the 23rd of August, 14.30
Place: Auditorium 54 N2C, Herlev University Hospital, Herlev Ringvej 75, DK-2730 Herlev
It would be nice to welcome you all
Professor Per thor Straten
Director
Abstract
"Immune Risk Profile" in cancer and ageing?
Professor Graham Pawelec, head of the Tübingen Tumour Immunology and Ageing Group (TATI), University of Tübingen
Adaptive immunity shows signs of "exhaustion" under situations of chronic antigenic stress – persistent infections, autoimmunity and cancer may all exacerbate dysregulation and malfunction of immunity. Longitudinal studies in humans have begun to reveal biomarkers of immune ageing ("immune signatures") increasingly recognized as an "immune risk profile", or IRP, predicting mortality in the very elderly. The IRP defines biomarkers of immune ageing ("immunosenescence") to which persistent infection with the B-herpesvirus HHV5 (Cytomegalovirus, CMV) materially contributes. Whether other persistent antigens, such as tumour antigens, might also cause IRP-like immune alterations, and whether these would be exacerbated by CMV, is presently unclear. The decreased proportions of naïve CD8 cells and increases in late-differentiated cells that are a hallmark of the IRP are not seen in CMV-negative populations. However, neither the absolute number nor the proportion of naïve cells are part of the IRP, as determined on longitudinal studies. Thus, it is the accumulation of CD8 cells at late stages of differentiation that determines whether a person falls into the IRP group or not. A significant fraction of the human immune system is committed to controlling CMV, and this commitment increases with age in order to control persistent, reactivating CMV. It may itself cause pathology as a side effect, as a result of maintaining higher systemic levels of inflammatory mediators (which could also facilitate carcinogenesis) and decreasing the "immunological space" available for immune cells with other specificities. The hallmark parameters of the IRP are also associated with poorer responses to (influenza) vaccination, implying that their general vaccine responsiveness would be diminished, including to cancer vaccines. We are therefore currently exploring the interactions between cancer, CMV infection, IRP parameters and vaccine responsiveness in prostate cancer, breast cancer and melanoma.
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Last update: August 12, 2010
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