Co-inhibitory/immune checkpoint receptors
The unprecedented clinical success of therapies that target co-inhibitory or immune checkpoint receptors in the treatment of multiple cancers has revolutionized the field of cancer immunology. Co-inhibitory receptors comprise a class of cell surface receptors that are up-regulated on activated T cells in order to contract pro-inflammatory T cell responses and prevent the unwanted consequences of uncontrolled inflammation. Unfortunately, co-inhibitory receptors have been co-opted in cancer such that their constitutive and high expression on T cells in tumor tissue dampens anti-tumor T cell responses. The Anderson lab has done pioneering research on the role of the co-inhibitory receptor Tim-3 in regulating anti-tumor immunity. Current research focuses on dissecting the role of Tim-3 and other co-inhibitory receptors in the regulation of different immune cell subsets in tumor tissue and elucidating how blockade of Tim-3 signaling alters the function of different immune cell subsets in the tumor microenvironment.
CD8 T cell dysfunction
CD8+ cytotoxic T cells are key to successful anti-tumor immunity. However, CD8+ T cells loose their functional efficacy in tumor tissue. A major research effort in the Anderson lab is to molecularly dissect the dysfunctional T cell state in cancer using transcriptomics and systems biology approaches.
Regulatory T cells
CD4+ FoxP3+ regulatory T (Treg) cells are major suppressors of anti-tumor immunity. The Treg cells that infiltrate tumor tissue up-regulate immune checkpoint receptors and exhibit a highly active and suppressive phenotype. A major research effort in the Anderson lab is to elucidate how checkpoint receptor pathways direct the function of Treg in tumor tissue.
Integrated into the above research efforts are the use of cutting-edge technologies such as CyTOF, single-cell transcriptomics, and genome-editing approaches. We have developed a custom mass cytometry platform to assess the landscape of co-stimulatory and co-inhibitory receptors in tumor tissue using CyTOF. In collaboration with investigators at the Broad Institute, we are using single-cell transcriptomics and systems biology approaches to unravel the molecular programs associated with dysfunctional CD8+ T cells and highly active Treg in cancer. We are further taking advantage of recent advances in genome-editing using CRISPR/Cas9 to elucidate how key molecular targets affect the anti-tumor T cell response.