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

Neoantigens 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 respon...

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Bibliographic Details
Main Authors: DuPage, Michel J., Mazumdar, Claire, Winslow, Monte M., Bronson, Roderick T., Crowley, Denise G., Chen, Jianzhu, Cheung, Ann, Schmidt, Leah Marie, Jacks, Tyler E.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2014
Online Access:http://hdl.handle.net/1721.1/92334
https://orcid.org/0000-0001-5785-8911
https://orcid.org/0000-0002-5687-6154
https://orcid.org/0000-0001-9076-8475
Description
Summary:Neoantigens 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.