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

Autor:	Fitzgerald B; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Connolly KA; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Cui C; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Fagerberg E; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Mariuzza DL; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Hornick NI; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Foster GG; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., William I; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Cheung JF; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA., Joshi NS; Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.; Lead contact.
Jazyk:	angličtina
Zdroj:	Cell reports methods [Cell Rep Methods] 2021 Sep 27; Vol. 1 (5). Date of Electronic Publication: 2021 Sep 16.
DOI:	10.1016/j.crmeth.2021.100080
Abstrakt:	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. Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.
Databáze:	MEDLINE
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