Abstract 6432: Melanoma-driven alterations in lipid and iron metabolism in the bone marrow niche

Abstract Melanoma is the deadliest form of skin cancer and age is a negative independent prognostic factor of overall survival for melanoma patients. Aging causes systemic changes, such as increased bone marrow (BM) adiposity and iron accumulation, which could impact the aged antitumor response. We hypothesize that elevated BM fat and iron due to aging promote immune dysfunction, weakening systemic antitumor defenses. We utilized flow cytometry to analyze melanoma- and age-related alterations to the BM and tumor immune cell composition. Our preliminary data suggest that mice challenged with melanoma systemically undergo myelopoiesis, resulting in an increase in myeloid cells in the BM; however, tumors of aged mice had increased myeloid cell infiltration. Conversely, the lymphoid compartment contracts in the BM of tumor-bearing mice, with reduced T and B lymphocytes and NK cells. Importantly, age- and tumor-related changes are not limited to immune cell population changes. Our data show significantly increased intracellular lipid accumulation in BM myeloid cells of tumor-bearing mice compared to control animals. However, analysis of overall lipid content in the BM from these mice shows a significant reduction of lipids in the BM niche, suggesting that myeloid cells in this niche might uptake the lipids from their environment. Increased lipid uptake and peroxidation has been linked with ferroptosis, an iron-dependent form of cell death. Utilizing a Prussian Blue stain, we show that intracellular iron increased in the BM of aged mice compared to young mice, suggesting the BM cells might be sequestering iron. Ultimately, there is an increased production of myeloid cells, an increase in intracellular lipids in myeloid cells as well as an increase in iron levels in the BM niche with aging and in the future, we would like to further explore ferroptosis in the BM niche. As a future direction, we would like to explore ferroptosis in the BM niche. These insights into lipid and iron metabolism in myeloid cells in the bone marrow niche will lead to a better understanding of the systemic response to melanoma and can inform future treatments for elderly patients with melanoma. Citation Format: Alexis Erasta Carey, Murilo Ramos Rocha, Cheyenne Palm, Vania Wang, Denys Balandin, Ethan Black, Kevin Zhang, Fan Huang, Ashani Weeraratna. Melanoma-driven alterations in lipid and iron metabolism in the bone marrow niche [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6432.