Expression of tumour-specific antigens underlies cancer immunoediting

Abstract

This paper illustrates that immunosurveillance and immunoediting can occur in an oncogene-driven endogenous tumour model provided that the tumours carry strong neoantigens not present in the host. Two groups reporting in this issue of Nature use contrasting approaches to come to many of the same conclusions about the process of cancer immunoediting, in which an individual is protected from cancer though the elimination and immunogenic modification of cancerous cells. Matsushita et al. use whole-exon sequencing of mouse sarcomas induced by chemical carcinogens to obtain evidence for T-cell-mediated immuno-selection as a mechanism of immune editing. DuPage et al. demonstrate that immunosurveillance and immunoediting can occur in an oncogene-driven endogenous tumour model provided that the tumours carry strong neoantigens that are not present in the host. 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 thereby enhanced in immune-compromised mice, whereas 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, in part because of the known antigenic complexity and heterogeneity of carcinogen-induced tumours4. Here we adapted a genetically engineered, autochthonous mouse model of sarcomagenesis to investigate the process of cancer immunoediting. This system allows us to monitor the onset and growth of immunogenic and non-immunogenic tumours induced in situ that harbour identical genetic and histopathological characteristics. By comparing the development of such tumours in immune-competent mice with their development in mice with broad immunodeficiency or specific antigenic tolerance, we show that recognition of tumour-specific antigens 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 presentation on major histocompatibility complex I was necessary and sufficient for this immunoediting process to occur. These results highlight the importance of tumour-specific-antigen expression in immune surveillance, and potentially, immunotherapy.