The landscape of cancer treatment has been fundamentally changed by advances in immunotherapy: bolstering or augmenting the body’s own defenses to attack and eliminate cancer cells. While some patients experience remarkable responses to these immunotherapies, most will not benefit. This highlights a major gap in our understanding, namely that we do not fully understand how the immune system is regulated at the tumor site. Cancer cells must fuel their constant division, and as such become metabolically ‘deregulated,’ depleting the local environment of nutrients and oxygen.
Dr. Delgoffe’s lab is exploring the idea that this metabolic landscape might hinder immunotherapy, as T cells infiltrating the tumor can essentially be ‘starved’ of the fuel needed for their activity. By diving deeper into the interplay between metabolic stress and immune dysfunction in cancer, Delgoffe’s team has found that while this nutrient dearth environment can suppress the function of healthy immune cells that may destroy tumors, other more dysfunctional types of immune cells can thrive in this altered state. He seeks to understand the precise metabolic pathways that support the survival of deleterious immune cells within tumors and develop metabolic reprogramming strategies that may function by eliminating these cells. Ultimately, he hopes the insights his team uncovers can pave the way for the development of improved cancer immunotherapy strategies that provide metabolic support to this revived immune response.
Projects and Grants
Reversing T Cell Dysfunction Through Metabolic Reprogramming
University of Pittsburgh School of Medicine | All Cancers | 2020
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