Autoimmune control of anti-tumor immunity
What is known about the genesis of memory T cell responses has historically been derived from studies of infectious pathogens. Memory T cell responses to tumors are typically difficult to generate because tumors are an altered form of self-tissue and the mechanisms by which they are maintained are not well understood. The Turk laboratory has made groundbreaking discoveries in the field such as establishing that autoimmune disease is a critical determinant for the maintenance of T cell memory to tumor/self antigens.
Our early studies demonstrated that depletion of a population of immunosuppressive cells called regulatory T cells (Treg), combined with surgical excision of primary tumors induces the development of long-lived, protective memory T cell responses to melanoma in mice. These studies demonstrated that memory T cell responses to tumor-expressed self-antigens can be generated in vivo. This work also established that Treg cells are a major barrier to the generation of anti-cancer memory T cells.
Our more recent work has shown that autoimmune melanocyte destruction (vitiligo) subsequent to depletion of Treg cells is required to maintain memory T cell responses that protect against melanoma. These studies demonstrate that antigen provided by dying melanocytes maintains T cells specific for melanoma, establishing a previously unrecognized role for autoimmunity in supporting immune responses to cancer. These findings led to collaborative studies with the Ernstoff Laboratory at Dartmouth to determine if vitiligo also enhances memory T cell responses in metastatic melanoma patients.
These studies establish that protective long-lived memory T cell responses to tumors can be achieved in vivo. Our goals are to define the specific mechanisms by which autoimmune vitiligo maintains T cell memory and to investigate how these T cells establish niches in peripheral tissue.
