A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma
| Autor: | Gena G. Foster, Ivana William, Julie F. Cheung, Brittany Fitzgerald, Nikhil S. Joshi, Can Cui, Kelli A. Connolly, Eric Fagerberg, Noah I. Hornick, Dylan L. Mariuzza |
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| Rok vydání: | 2021 |
| Předmět: |
integumentary system
business.industry medicine.medical_treatment T cell Immunotherapy medicine.disease medicine.disease_cause Biochemistry Genetics and Molecular Biology (miscellaneous) Biochemistry Immune checkpoint Article Computer Science Applications medicine.anatomical_structure Antigen Genetics medicine Cancer research Adenocarcinoma Cytotoxic T cell Radiology Nuclear Medicine and imaging KRAS business Lung cancer Biotechnology |
| Zdroj: | Cell reports methods |
| ISSN: | 2667-2375 |
| Popis: | SUMMARY 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. Graphical abstract In brief Fitzgerald et al. develop a mouse model of LUAD that generates an endogenous CD8 T cell response against lung tumors. Tumors from this model respond to immunotherapy, providing a new tool for researchers to use to investigate the processes that underlie immunotherapy responses. |
| Databáze: | OpenAIRE |
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