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

被引：19

作者：

Fitzgerald, Brittany ^{[1
]}

Connolly, Kelli A. ^{[1
]}

Cui, Can ^{[1
]}

Fagerberg, Eric ^{[1
]}

Mariuzza, Dylan L. ^{[1
]}

Hornick, Noah, I ^{[1
]}

Foster, Gena G. ^{[1
]}

William, Ivana ^{[1
]}

Cheung, Julie F. ^{[1
]}

Joshi, Nikhil S. ^{[1
]}

机构：

[1] Yale Univ, Dept Immunobiol, Sch Med, New Haven, CT 06519 USA

来源：

CELL REPORTS METHODS | 2021年 / 1卷 / 05期

关键词：

K-RAS; TRANSGENIC MICE; TUMOR MICROENVIRONMENT; CHECKPOINT BLOCKADE; LENTIVIRAL VECTOR; CRE RECOMBINASE; C-MYC; CANCER; GROWTH; EXPRESSION;

D O I：

10.1016/j.crmeth.2021.100080

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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 KP3NINJA (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 infectioninduced 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.

引用

页数：18

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