From cancer immunosurveillance to cancer immunotherapy

In response to oncogenic threats, tumor suppressor mechanisms that halt cell-cycle progression can stimulate immunemediated destruction of pre-malignant and malignant cells. Accordingly, defining the molecular interactions between tumor suppressor pathways and cancer immunity may be instrumental in the development of novel cancer therapies. We here discuss the immunological consequences of cellular senescence and apoptosis in the context of tumorigenesis. We then review the literature on potential danger signals' that may link tumorigenesis and cancer immunosurveillance and discuss the range of immune-regulatory mechanisms that restrict cancer immunity. Finally, we discuss how a better understanding of the interacting pathways governing cell death, danger, and immunity may lead to the development of effective cancer immunotherapies. We propose that the minimum requirements for the induction of clinically relevant immune responses include, on the one hand, the development of therapeutic drugs that can either bypass or rescue intrinsic tumor suppressor pathways while inducing a pro-immunogenic form of cell death and, on the other hand, the concerted combination of immune-stimulatory agents able to enhance tumor-antigen presentation and overcome critical immune-regulatory checkpoints that restrict cancer immunity.