Immune Characterization of High-Grade Bladder Cancer

Project: Research project

Description

In the United States, urothelial carcinoma (UC) of the bladder is the fourth most common malignancy in men and ninth most common in women with 72,570 new cases and 15,210 deaths expected in 2013. Bladder cancer can be divided into low-grade and high-grade tumors. While patients with low-grade tumors uniformly have a good prognosis, those with high-grade tumors clinical outcome is much worse and much more varied (so called heterogeneous). To better understand the heterogeneity within high-grade bladder cancer we examined the expression patterns of genes within a large group of high-grade, muscle-invasive bladder tumors and found that there are two distinct classes of bladder tumors that can be distinguished by their gene expression patterns but not by other means such as histology. Because of their similarity to several of the expression subtypes of breast cancer we have named the “basal” and “luminal” and developed a gene expression classifier consisting of 47 genes (BASE47) that can accurately distinguish basal and luminal bladder cancer. One of the most prominent differences between basal and luminal bladder cancers is that basal-like bladder tumors express high levels of genes associated with inflammation and in particular genes involved with suppressing the body’s immune response (e.g. PD-L1, CTLA4, IDO1, FOXP3). Because of the recent clinical success in subsets of patients of using antibodies that block these pathways (ie. anti-PD-L1 and anti-CTLA antibodies) to enhance the tumor directed immune response, the area of tumor immunotherapy has garnered much attention and excitement. For example, it was named Science magazine’s scientific breakthrough of the year (http://news.sciencemag.org/breakthrough-of-the-year-2013). Based on our studies to date we hypothesize that bladder cancer, and in particular basal-like bladder tumors, will be especially responsive to tumor immunotherapy. Our studies will 1) precisely characterize the immune infiltrate from human tumors. 2) use Next Generation sequencing to determine the whether the immune cells present in the tumor are targeting a specific tumor protein or many tumor proteins. And 3) use preclinical mouse models to assess the effects of immunotherapy antibodies in clinical development.
StatusFinished
Effective start/end date7/15/147/14/16

Funding

  • Bladder Cancer Advocacy Network

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Urinary Bladder Neoplasms
Neoplasms
Immunotherapy
Gene Expression
Genes
Antibodies
Anti-Idiotypic Antibodies
Histology
Urinary Bladder
Proteins
Breast Neoplasms
Inflammation
Carcinoma
Muscles