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

Brittany Fitzgerald, Kelli A. Connolly, Can Cui, Eric Fagerberg, Dylan L. Mariuzza, Noah I. Hornick, Gena G. Foster, Ivana William, Julie F. Cheung, Nikhil S. Joshi

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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 languageEnglish (US)
Article number100080
JournalCell Reports Methods
Volume1
Issue number5
DOIs
StatePublished - Sep 27 2021
Externally publishedYes

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

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