Craig L. Slingluff, Jr., MD, CRI CLIP Investigator University of Virginia Health System Area of Research: Melanoma Melanoma is the 5th most common cancer in the US, with almost 100,000 new diagnoses in 2022 alone. In patients with melanoma arising from the skin, the most common first place it can spread (metastasize) is to a nearby lymph node. The standard management for patients with melanoma that has spread to palpable or visible lymph nodes involves surgically removing both the tumor-involved lymph nodes and the normal (tumor-free) lymph nodes, even when melanoma is detected in only one lymph node. Such surgical removals often result in patient suffering and long-term disabilities. Therefore, Dr. Slingluff is proposing to test whether it is better to preserve the tumor-free lymph node and to remove only the enlarged node which, in addition to reducing patient suffering and morbidity, may improve immune-mediated control of the melanoma. Dr. Slingluff will take advantage of a novel human tissue resource of tumor-involved and tumor-free nodes from the same patients with known reactivity to defined melanoma antigens, using methods to identify the melanoma-reactive T cells and to understand their function. This project will test the hypotheses that the tumor-free nodes in the same lymph node basin are enriched with immune cells (T cells) reactive to melanoma antigens and that tumor-reactive T cells in the tumor-free nodes are more functional than those in the tumor-involved nodes. The data retrieved from Dr. Slingluff’s work would support a potential immunotherapeutic benefit of leaving tumor-free nodes in place at surgery for patients with melanoma who are being treated with systemic PD-1 antibody immunotherapy in the neoadjuvant and adjuvant settings. Dr. Slingluff’s research aims to deepen our understanding of the immune response to melanoma and the behavior of melanoma-reactive T cells. This research could potentially lead to groundbreaking advancements in the management of melanoma, paving the way for more precise and personalized treatment strategies. Projects and Grants Antitumor immunity in tumor-free and tumor-involved lymph nodes of patients with stage III melanoma University of Virginia Health System | Melanoma | 2023 A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers (NCT02643303) University of Virginia Health System | Bladder Cancer, Breast Cancer, Head and Neck Cancer, Kidney Cancer, Lymphoma, Melanoma, Other Cancer, Prostate Cancer, Sarcoma, Skin Cancer | 2015 Effects of vaccine adjuvants and skin microbiome in the vaccine-site microenvironment University of Virginia Health System | All Cancers | 2020 Barrier Molecules and Their Impact on T cell Infiltration in Melanoma University of Virginia Health System | Melanoma | 2017 Retention integrins: induction and function on cancer-reactive T lymphocytes University of Virginia Health System | Lung Cancer, Melanoma | 2015 Immunotherapeutic targeting cell surface neoantigen SAS1B University of Virginia Health System | Kidney Cancer, Pancreatic Cancer | 2015
