Discovery of Regulatory Molecules on T Regulatory cells

Discovery of Regulatory Molecules on T Regulatory cells Discovery of Regulatory Molecules on T Regulatory cells Project Summary: Recently, a few monoclonal antibody treatments targeting the immune system have shown promising results in trials involving patients with advanced cancer. Specifically anti-CTLA-4, anti-PD-1 and anti-PDL-1 have been used to block suppressive T cells in cancer patients with impressive clinical results. Various populations of lymphocytes with immune suppressive functions may have cell surface molecules that can serve as targets of monoclonal antibodies (CTLA-4, PD-1 and PD-1L. New research tools provide the ability to isolate T cells from tumors with regulatory function. Antibodies against these suppressive molecules may allow cytolytic lymphocytes to retain anti-tumor activity by blocking negative signals that suppress the killing activity of anti-tumor lymphocytes. We will study cell surface markers and cellular characteristics of regulatory lymphocytes infiltrating tumors and in peripheral blood from advanced cancer patients. The hypothesis driving this exploratory study is that regulatory T cells (Tregs) infiltrate tumors and can be found in peripheral blood from patients with cancer. Isolation of peripheral and tumor-derived Tregs will allow us to study the immune-suppressive qualities of these cells. We propose the following aims: 1. Isolate Tregs from tumor and peripheral blood from cancer patients 2. Compare the immune suppressive capacity of peripheral and tumor-derived Tregs 3. Evaluate membrane fractions by LC-MS/MS for novel markers found on Tregs, not found on non-Tregs.