Endogenous T Cell Responses to Antigens Expressed in Lung Adenocarcinomas Delay Malignant Tumor Progression

SummaryNeoantigens derived from somatic mutations in tumors may provide a critical link between the adaptive immune system and cancer. Here, we describe a system to introduce exogenous antigens into genetically engineered mouse lung cancers to mimic tumor neoantigens. We show that endogenous T cells respond to and infiltrate tumors, significantly delaying malignant progression. Despite continued antigen expression, T cell infiltration does not persist and tumors ultimately escape immune attack. Transplantation of cell lines derived from these lung tumors or prophylactic vaccination against the autochthonous tumors, however, results in rapid tumor eradication or selection of tumors that lose antigen expression. These results provide insight into the dynamic nature of the immune response to naturally arising tumors.

Graphical AbstractFigure optionsDownload high-quality image (231 K)Download as PowerPoint slideHighlights
► T cell responses against autochthonous lung tumors delay malignant progression
► Antitumor T cells lack optimal function due to incomplete priming
► In contrast, transplantable lung tumor models prime protective T cell responses
► Vaccination against antigens in autochthonous tumors promotes tumor protection