Kurzfassung

Understanding the impact of ageing on non-efficient tumor immune responses is the basis for the identification of new molecular targets whose modulation could improve the success of directed immunotherapies. Systemic signals secreted by cells with the senescence-associated secretory phenotype (SASP) can impair protective immunity against malignant cells and pathogens. In a mouse model of hepatocyte-specific deletion of the longevity gene Sirt6 we will analyze epigenetic alterations related to...Understanding the impact of ageing on non-efficient tumor immune responses is the basis for the identification of new molecular targets whose modulation could improve the success of directed immunotherapies. Systemic signals secreted by cells with the senescence-associated secretory phenotype (SASP) can impair protective immunity against malignant cells and pathogens. In a mouse model of hepatocyte-specific deletion of the longevity gene Sirt6 we will analyze epigenetic alterations related to SASP as well as the immunologic consequences of an aged hepatocyte environment to anti-tumor immune responses. Based on the fact that epigenetic alterations are reversible events, which make them attractive for therapeutic modulation, we will screen for compounds attenuating the ageing-related phenotype of Sirt6-deficient hepatocytes.
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