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Publication : A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma.

First Author  Fitzgerald B Year  2021
Journal  Cell Rep Methods Volume  1
Issue  5 PubMed ID  34632444
Mgi Jnum  J:360726 Mgi Id  MGI:7850867
Doi  10.1016/j.crmeth.2021.100080 Citation  Fitzgerald B, et al. (2021) A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma. Cell Rep Methods 1(5)
abstractText  Kras-driven lung adenocarcinoma (LUAD) is the most common lung cancer. A significant fraction of patients with Kras-driven LUAD respond to immunotherapy, but mechanistic studies of immune responses against LUAD have been limited because of a lack of immunotherapy-responsive models. We report the development of the immunogenic KP x NINJA (inversion inducible joined neoantigen) (KP-NINJA) LUAD model. This model allows temporal uncoupling of antigen and tumor induction, which allows one to wait until after infection-induced inflammation has subsided to induce neoantigen expression by tumors. Neoantigen expression is restricted to EPCAM+ cells in the lung and expression of neoantigen was more consistent between tumors than when neoantigens were encoded on lentiviruses. Moreover, tumors were infiltrated by tumor-specific CD8 T cells. Finally, LUAD cell lines derived from KP-NINJA mice were immunogenic and responded to immune checkpoint therapy (anti-PD1 and anti-CTLA4), providing means for future studies into the immunobiology of therapeutic responses in LUAD.
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