Expression of tumour-specific antigens underlies cancer immunoediting

Abstract

Cancer immunoediting is a process by which immune cells, particularly lymphocytes of the adaptive immune system, protect the host from the development of cancer and alter tumour progression by driving the outgrowth of tumour cells with decreased sensitivity to immune attack1,2. Carcinogen-induced mouse models of cancer have shown that primary tumour susceptibility is enhanced in immune-compromised mice, while conversely, the capacity for such tumours to grow after transplantation into wild-type mice is reduced2,3. However, many questions about the process of cancer immunoediting remain unanswered due, in part, to the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we have adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allowed us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbor identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice to mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens (TSAs) by lymphocytes is critical for immunoediting against sarcomas. Furthermore, primary sarcomas were edited to become less immunogenic through the selective outgrowth of cells that were able to escape T lymphocyte attack. Loss of tumour antigen expression or MHCI presentation was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of TSA expression in immune surveillance, and potentially, immunotherapy.