Abstract 71: Melanoma alters the bone marrow immune composition in an age-related manner

Abstract

Abstract Melanoma accounts for the most skin cancer-related deaths in the United States. As patients age, anti-tumor responses decline, making age a negative independent prognostic factor of overall survival in melanoma. Despite advances in immunotherapeutic modalities, there remains a subset of patients who do not benefit from these treatments. Understanding cancer and age-related changes to immune cell development in the bone marrow can improve patient outcomes. We hypothesize that during aging, the bone marrow niche is reshaped, driving precursor cells to become immunosuppressive. This ultimately decreases the anti-tumor response to melanoma due to the skewing of hematopoiesis to yield decreased immune function. In order to tackle this hypothesis, flow cytometry was used to analyze immune compositional changes in the bone marrow of mice challenged with melanoma. Our preliminary data suggests that when melanoma is present in the skin, there are changes to the bone marrow niche, such as an increase in total myeloid cells. Specifically, in the bone marrow of aged tumor-bearing mice, we see a decrease in Ly6C+Ly6G+ granulocytic progenitor cells and an increase in Ly6C+Ly6G- monocytic progenitor cells compared to the bone marrow of young tumor-bearing mice. We predict that the secretome of the aged bone marrow niche will impact immune cell development by producing more immature myeloid cells that can travel to the tumor site. We also saw an increase in the proportion of CD4+ T-cells in the aged bone marrow when melanoma is present. Thus, there appears to be a shift in cell populations in the aged bone marrow niche when the mice are burdened with melanoma. As a future direction, we plan to investigate the role of the aged bone marrow niche and its secretome on the effectiveness of immunotherapies, such as anti-PD-1. These insights could lead to improved outcomes for elderly patients with melanoma. Citation Format: Alexis Erasta Carey, Yash Chhabra, Ethan Black, Murilo Ramos Rocha, Mitchell Fane, Vania Wang, Daniel Zabransky, Gloria Bravante, Laura Hueser, Ashani Weeraratna. Melanoma alters the bone marrow immune composition in an age-related manner [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 71.