Identification and Peripheral Tracking of Melanoma-Specific T Cells After Early-Stage Melanoma Diagnosis for Detection of Recurrence or Metastasis
Abstract
My career plans are, and always have been, focused on the connections between things. I am most interested in studying the interaction between melanoma and the immune system. Because connecting basic science to clinical medicine is the central goal of my career, I pursue the study of that interaction through working, both as a dermatologist and as a scientist. Developing myself as a physician both gives me insight into what is actually needed for patient care and keeps me connected to the patients that inspire my research. That research, in return, provides me with the potential to push forward patient care both for my own patients and for all people with melanoma. My career development and sustainment plan are centered around developing the interaction between these two aspects of my professional life, and it will be guided by a like-minded and highly accomplished researcher in my Career Guide, Dr. Sancy Leachman. Through the support and collaboration that the Melanoma Academy can provide, I would be able to rapidly accelerate my research, it would also provide me with scientific connections and perspectives that will shape and direct my contributions to where they will be of most use to the melanoma research field, and thereby to melanoma patients. The work outlined in this proposal is directed at the Focus Area challenge to develop prediction and surveillance tools for distinguishing patient populations at risk for second primary/recurrence and/or metastasis. I propose to meet this challenge by making use of immune cells that respond to melanoma, but are not able to eliminate it, in order to detect the presence of recurring or metastasizing melanoma before it would otherwise be recognized. This work will most directly benefit the many patients who are diagnosed with an early melanoma and need regular monitoring thereafter to detect possible recurrence or progression of their disease. The tools I plan to develop would provide additional means of monitoring and would enable melanomas that come back to be caught and treated earlier than is currently possible. The human immune system has been refined continually throughout our evolutionary history and, as we now appreciate, plays an important role in protecting us from cancers as they begin to develop. It is only those cancers that are able to elude or escape from the immune system that eventually cause disease. Recent work, driven by the success of immune-stimulating medications in treating melanoma, has identified that, in the majority of disease-causing cancers, the immune system recognizes the malignant tissue but is unable to mount a successful response. Because the immune cells that respond to a tumor are defined by their ability to not only recognize a problem, but copy themselves so that the problem can be addressed again in the future, detecting the presence of cells that are copies of cells recognizing a melanoma is a way to assess whether there is additional melanoma present in a person. Because these cells circulate throughout the body to monitor for disease, they are detectable in blood, which presents an opportunity to monitor patients for progressive or recurrent melanoma after an initial melanoma diagnosis and surgery. The difficulties in using these melanoma-targeted cells to monitor patients after a melanoma is found have, in large part, been due to the difficulty in identifying which cells are responding to melanoma. New technological advances have provided a set of tools that can be used to distinguish with more precision which cells in a person’s original melanoma biopsy are the tumor-responsive cells that may be useful for monitoring. The work described in this proposal will leverage those tools to look for tumor-responsive immune cells in early melanoma biopsies, and then monitor the blood of patients over time. If our hypothesis is correct, levels of tumor-responsive cells will increase over time in the context of recurring or pr
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310662
Entities
People
- Noah Hornick
Organizations
- Oregon Health & Science University
- United States Army