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Biomarkers to Predict Melanoma Patient Immunotherapy Outcomes

David Soto-Pantoja, PhD

Award Type Established Investigator Award
Institution Wake Forest University

Our immune system operates on a balance of cells that that can destroy infected or cancerous tissue with those that prevent attacking healthy tissue. This equilibrium is affected during cancer where cells that attack the tumor become inefficient allowing further growth, cancer spread (metastasis) and eventual demise of the patient. To address this problem researchers have developed drugs known as immune checkpoint inhibitors. These drugs re-invigorate cells known as T cells to attack the tumor. In patients with advanced melanoma treated with monoclonal antibodies targeting these immune checkpoints, 3-year survival increased by about 20%. However due to these drugs tipping the balance to a more hyperactive immune system it can cause side effects that are detrimental to the patient causing disruptions in treatment plans and efficacy. Currently methods are limited to predict or treat these side effects without limiting efficacy of the drugs therefore there is a great need to understand how these side effects emerge. The tumor microenvironment consumes aberrant levels of nutrients and release factors that can be felt by circulating cells. We believe that these changes can be sense by mitochondria which is the organelle in cells that regulates energy consumption. With new technological advancements we can measure how this organelle changes in function in patients. Our approach allows the bulk analysis of patient cells to test how their metabolism is affected as a consequence of immunotherapy. We theorize that patients that will develop side effects will also have a lower bioenergetic status. Our analysis will provide a marker to predict side effects before they develop and study genes that regulate metabolism to design clinical trials aimed at reducing the onset of side effects providing a personalized approach to improve outcomes in melanoma patients undergoing immune checkpoint therapy while preserving their quality of life.