Abstract

Dissecting Mechanisms of PD-1 Blockade with Massively Parallel Single-Cell RNA-Sequencing

Brian Miller, Oncology Fellow, Dana-Farber Cancer Institute

Anti-PD-1 antibodies are currently the most broadly applicable immunotherapy available for patients. However, even for the most sensitive cancers, less than 40% of patients respond to this therapy. Despite its clinical utility, the mechanisms of action of anti-PD-1 treatment are not fully known, limiting the rational design of combination therapies to increase its efficacy. The goal of my research is to understand the mechanisms by which anti-PD-1 therapy augments the anti-tumor immune response. We have developed a novel technology in massively parallel single-cell RNA-sequencing to interrogate the immune response to cancer. Using this technology, we can measure the expression of thousands of genes in hundreds to thousands of individual cells. This allows us to obtain a comprehensive understanding of the immune response to cancer by examining in great detail both common and rare cell types in the tumor microenvironment. We are studying how anti-PD-1 therapy alters populations of cells and their activation within the tumor microenvironment.