Abstract
Abstract Melanoma is responsible for the most skin cancer-related deaths in the United States. Melanoma occurrence and severity increase with age while the anti-tumor responses decrease. There have been robust responses to immunotherapy treatments, however, there remains a subset of patients who do not benefit from these modalities. Understanding more about immune cell development and age-related changes in the bone marrow can improve patient outcomes. Our hypothesis suggests that during aging, changes in Wnt signaling reshape the aged bone marrow niche, driving precursor cells to become suppressive. This ultimately decreases the anti-tumor response to melanoma due to the skewing of hematopoiesis to yield decreased immune function. In a young and aged setting, we assess the effect of a Wnt inhibitor, sFRP1, on the development of immune cell subtypes by using flow cytometry. We have preliminarily observed in situ that sFRP1 is increased in the aged bone marrow through immunohistochemical staining. We also saw a decrease in CD4 and CD8 T-cells and an increase in CD11b positive myeloid cells in the tumors of young mice treated with recombinant sFRP1 compared to age-matched mice treated with PBS by using immunohistochemical staining. We hypothesize that the increase in sFRP1 in the bone marrow niche will impact immune cell development in the niche and the immune response at the tumor site. As a future direction, we plan to investigate combination treatments of anti-sFRP1 with immunotherapies, such as anti-PD-1. These insights could lead to improve outcomes for elderly patients with melanoma. Citation Format: Alexis Erasta Carey, Yash Chhabra, Mitchell Fane, Laura Hueser, Gloria Marino, Daniel Zabransky, Ashani Weeraratna. Impact of the aged bone marrow on the anti-tumor response to melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2554.
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