Since decades cancer immune surveillance is a topic of hot debates and
there is still controversy about the role of the immune system in
controlling tumor growth and eliminating transformed cells. For viral
induced cancers it has been shown that the immune system is able to
surveil tumor growth, but it remains unclear whether sporadic cancers
are recognized by immune cells resulting in a destructive T cell
response. This study investigated de novo T cell responses against a
neoantigen expressed by cancer cells under non-acute inflammatory
conditions. Therefore, a novel transplantation mouse model was
established which closely simulated human sporadic cancer development.
In this model, expression of the cancerdriving antigen and oncogene was
tightly regulated by the Tet system. Cancer cells could be reversibly
arrested after switching off the oncogene/antigen, but, surprisingly,
the oncogene/antigen could be reexpressed at later time points in vitro
and in vivo. By applying this model, the question at which time point
during tumorigenesis the immune system interacts with nascent cancer
cells was answered. Results of this study demonstrated that
neoantigenspecific CD8^{+T cells were induced in the absence of acute
inflammation and rejected nascent cancer cells thereby strongly arguing
for existence of immune surveillance. The relevance of direct priming
for inducing cytotoxic T cell responses against neoantigens expressed by
sporadic cancer was confirmed by further experiments of this study.
