Ricerc@Sapienza

Human papillomaviruses (HPV) are the causative agent of squamous cervical carcinoma. The HPV-associated transformation is a multistep process that can occur after several years from the infection. During this time HPV can alter proliferation and other numerous mechanisms of the infected cell, mainly through the action of E6 and E7 proteins. Exploitation of the tumor microenvironment (TME) to impair immune response is an important feature of HPV-associated tumorigenesis even if the complexity and the plasticity of the TME offer compelling reasons to hypothesize some other roles. Damage associated molecular patterns (DAMPs) are a large family of autologous molecules that convey "danger signals" from both stressed and death cells. A specific inflammatory response arises when the right signal is sensed from the right receptor. High mobility group box 1 (HMGB1) is a non-histone nuclear protein that is passively released extracellularly by necrotic cells or actively secreted by activated immune cells. Once in the extracellular environment, it can bind different receptors thereby activating pro- or anti-inflammatory responses, depending by the context. Since HPV-related carcinogenesis is an invasive and stressful process that lasts some years, it is reasonable to suppose that DAMPs can participate at the HR-HPV persistent infection. Based on previous data showing that HR-HPV transformed keratinocytes can build an immunosuppressive TME, the purpose of this project is to evaluate the possible involvement, with anti-inflammatory role, of HMGB1 in a high-risk (HR)-HPV-positive cellular model. The objective of the project is to define new-insight into the DAMPs role in the HPV-related tumorigenesis.