Damon Runyon Researchers

Immunotherapies that take the brakes off the immune response and direct cytotoxic T lymphocytes (CTLs) to hunt down tumors have revolutionized cancer treatment in the last decade. Stories of patients who are cured by immunotherapy even after exhausting all other treatment options are increasingly common – but unfortunately, only a minority of patients achieve such remarkable benefits. Now, two pressing challenges are to understand why immunotherapy fails in non-responders and to develop new or modified therapies that achieve durable remission for these patients as well. Successful immunotherapy is predicated on the infiltration of the tumor microenvironment by tumor-specific CTLs. The cells and signals that generate and sustain these cells are collectively known as type 1 immunity. Conversly, the immune cells and signals associated with the distinct processes of tissue remodeling and wound healing are known as type 2 immunity. At best, a tumor microenvironment dominated by a type 2 immune response precludes a robust type 1 response, but there is also evidence that the type 2 response may actually promote tumor growth and survival. The success of cancer immunotherapy may therefore rely in part on preventing type 2 responses. The goal of this work is to understand the regulation of type 2 immune responses, with a particular focus on the earliest events that lead to initiation of type 2 immunity. It is our hope that insights gained from these studies will inform that development of improved cancer immunotherapies that guide immune responses away from type 2 towards type 1.