Chi3l1 Regulation of Checkpoint Regulating, Costimulatory, and Coinhibitory Molecules in Primary and Metastatic Lung Cancer
Abstract
Chitinase 3-like 1 (Chi3l1; also called BRP-39 in the mouse and YKL-40 in man), the prototypic CLP, is expressed in an exaggerated fashion in a variety of diseases characterized by inflammation, injury and remodeling. The levels of Chi3l1 are also increased the serum and or tissues from patients with a variety of cancers including lung cancerand their levels are inversely correlated with prognosis of the patients. However, the role(s) of Chi3l1 in the pathogenesis of lung cancer have not been defined. To begin to address this issue, we generated Chi3l1 null mutant (Chi3l1-/-) and lung-specific YKL-40 overexpressing (OE) transgenic (YKL40 Tg) mice and evaluated them in models of metastatic and primary lung cancer. Preliminary studies using animal models of primary and metastatic lung cancer and Chi3l1 neutralizing antibody demonstrated that Chi3l1 plays an essential role in the regulation of immune checkpoint inhibitors (ICPs) and T cell co-stimulatory molecules. In the first year of grant period, we made a substantial progress in the following areas: 1) Successful generation and preclinical application of effective neutralizing antibodies against Chi3l1 that demonstrated an impressive inhibitory effect on melanoma lung metastasis as well as the primary lung cancer. 2) Effect of Chi3l1 in tumor infiltrating macrophages and CD8 Tcells in metastatic and primary lung cancer and its regulation of immune check point inhibitor molecules, such as PD-1 and PD-L1, expression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2018
- Accession Number
- AD1060408
Entities
People
- Chun G. Lee
- Jack A. Elias
Organizations
- Brown University