Deregulation of innate and adaptive immune responses in human papillomavirus infection and cancer

Abstract

HPVs need to avoid immune responses of the host in order to establish persistent infection. HPVs achieve this by dampening innate immunity of keratinocytes, the major cell type targeted by HPV. As there is reduced production of danger signals including antimicrobial molecules, proinflammatory cytokines and chemokines by keratinocytes, HPV infection remains undetected by the immune system. However, our further data showed that PRR signaling is not completely blocked by hrHPV. Thus, the activation of innate and adaptive immunity at the site of HPV infection is slowed down but not prevented. In order for cancers to grow out they need to suppress the local effector cells. We focused on the role of the PD-1 receptor and its ligands PD-L1 and PD-L2, our data showed that the majority (81%) of the tumors from cervical cancer patients do not express PD-L1. Furthermore, PD-L1 expression was not associated with patient survival. Finally, we presented evidence that the chemokine receptor CXCR7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients.