Colorectal Cancer Immunotherapy by Pharmacological Suppression of Liver X Receptor Activity
Abstract
Colorectal cancer is a leading cancer diagnosis for men and women as there are 1 million new diagnosed patients every year. Cancer cells are known to secrete lipid metabolites that prevent the immune system from mounting a full antitumor response. These lipids activate the liver X receptor (LXRs) nuclear receptors that regulate lipid and carbohydrate metabolism, and immune function. One of the key cell types involved in initiating an anti-tumor response is the dendritic cell. A healthy dendritic cell probes the intracellular spaces, blood stream and lymphatic system for molecular fragments or antigens that indicate that diseased tissues, infection or tumor growth is present. If tumor growth is detected, dendritic cells will migrate to lymph nodes and present tumor associated antigens and secrete cytokines that are used to stimulate the activity of T-cells.These activated T-cells then migrate to the site of the tumor and commence destruction of any tumor cell baring the relevant tumor associated antigens. Tumor cells secrete ligands; lipid metabolites that activate the Liver-X-Receptor in dendritic cells and prevent dendritic cell migration to lymph nodes. In addition, lipid accumulation in the tumor microenvironment inhibit macrophage and T-cell activity. This is called tumor masking or immune evasion.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2018
- Accession Number
- AD1056829
Entities
People
- Katherine J. Carpenter
Organizations
- Saint Louis University