Abstract B32: Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice

Autor: Walter J. Jessen, Eva Dombi, Tilat A. Rizvi, Nathan Salomonis, Kashish Chetal, Mi-Ok Kim, Jianqiang Wu, Nancy Ratner, Jay Pundavela, Jonathan S. Fletcher
Rok vydání: 2020
Předmět:
Zdroj: Cancer Immunology Research. 8:B32-B32
ISSN: 2326-6074
2326-6066
DOI: 10.1158/2326-6074.tumimm18-b32
Popis: Plexiform neurofibroma is a major contributor to morbidity in neurofibromatosis type I (NF1) patients. Macrophages and mast cells infiltrate neurofibroma, and data from mouse models implicate these leukocytes in neurofibroma development. Anti-inflammatory therapy targeting these cell populations has been suggested as a means to prevent neurofibroma development. Here, we compare gene expression in inflamed nerves from NF1 models that invariably form neurofibroma to those with inflammation driven by EGFR overexpression, which rarely progresses to neurofibroma. We find that the chemokine Cxcl10 is uniquely upregulated in NF1 mice that invariably develop neurofibroma. Global deletion of the Cxcl10 receptor Cxcr3 prevented neurofibroma development in these neurofibroma-prone mice. Cxcr3 expression localized to T cells and dendritic cells (DCs) in both inflamed nerves and neurofibromas. These data support a heretofore unappreciated role for T cells/DCs in neurofibroma initiation. Citation Format: Jonathan S. Fletcher, Jianqiang Wu, Walter J. Jessen, Jay Pundavela, Eva Dombi, Mi-Ok Kim, Tilat A. Rizvi, Kashish Chetal, Nathan Salomonis, Nancy Ratner. Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B32.
Databáze: OpenAIRE