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.

Cutting-edge Technologies

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.