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 cancer and 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. In the two years of grant period, we accomplished most of the major goals that we initially proposed. In this project, we successfully demonstrated that: 1) the regulatory role and mechanism of Chi3l1 in the expression of immune checkpoint molecules and its effect on tumor infiltrating immune cells in metastatic and primary lung cancer, 2) impressive therapeutic effect of anti-Chi3l1 neutralizing monoclonal antibody treatment on the development and or progression of melanoma lung metastasis and primary lung cancer, 3) the significant inhibitory effect of Poly(I:C), a strong RLH stimulant, in the development or progression of primary lung cancer, 4) a significant association between the serum or tissue levels of Chi3l1 and the clinical course of the primary lung cancer patients.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1086368
Entities
People
- Chun G. Lee
- Jack A. Elias
Organizations
- Brown University