Abstract
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 × 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.
Original language | English (US) |
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Article number | 100080 |
Journal | Cell Reports Methods |
Volume | 1 |
Issue number | 5 |
DOIs | |
State | Published - Sep 27 2021 |
Externally published | Yes |
Keywords
- GEMM
- T cell
- lung adenocarcinoma
- neoantigen
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- Genetics
- Radiology Nuclear Medicine and imaging
- Computer Science Applications