Abstract 5518: Tumor immune microenvironment of bone marrow metastasis in patients with solid tumor
Authors: Saijo Asaki , Kinowaki Keiichi , Yamamoto Kazumasa , Watanabe Shogo , Takemura Kohji , Yamaguchi Takeshi , Tanabe Yuko , Suyama Koichi , Yano Hiromu , Komohara Yoshihiro , Miura Yuji 
Published: March 2024

Abstract
Background: The tumor immune microenvironment plays a crucial role in tumor progression and treatment outcomes, both at the primary tumor site and metastatic sites. Metastatic growth within the bone marrow (BM) is relatively infrequent. Despite its unique immunological characteristics, there is a paucity of research on tumor immune microenvironment in the context of BM metastasis, particularly in patients with solid cancer. This study aims to elucidate the dominant immune cell populations within the BM of patients with solid cancer BM metastasis.
Materials and Methods: Patients with solid tumors, who underwent BM examinations (aspiration and/or biopsy) for suspected BM metastasis at our institution between 2016 and 2023 were extracted from the database of pathology. To evaluate BM immune microenvironment in patients with BM metastasis originating from solid tumor, we performed flow cytometry analysis of myeloid and lymphoid subsets using bone marrow aspiration. Myeloid-derived suppressor cells (MDSCs) were defined as CD33+CD14+HLA-DR-/low. Additionally, a control group was established, consisting of patients in whom BM metastasis were pathologically ruled out.
Results: The study involved the BM examinations in 39 patients, 22 of whom were pathologically diagnosed with BM metastasis. No substantial difference in age or gender were observed between patients with or without BM metastasis. However, the incidence of bone metastasis was significantly higher in the BM metastasis group compared to the non-BM metastasis group (90.9 vs. 47.1%, P=0.004). The median duration from the initial diagnosis of metastatic state to the occurrence of BM metastasis was 14.5 days (range 0 - 2194 days) for patients with BM metastasis, whereas it was 170 days (range 0 - 1304 days) for those without BM metastasis. Among the patients who underwent BM examinations, flow cytometry analysis was available in 13 patients with BM metastasis and 11 patients without BM metastasis. Our analysis revealed that a substantial increase in the mean percentage of MDSCs (CD14+HLA-DR-/low) in CD14+ monocytes of BM aspirates from patients with BM metastasis compared to those without (28.06 vs. 8.09%, P=0.0005). Additionally, while not statistically significant, the mean percentage of CD3+ T cells in the total live cell population appeared to be higher in patients with BM metastasis compared to those without (10.26 vs. 6.67%, P=0.0622). In terms of lymphoid subsets, CD4/8 ratio was significantly elevated in patients with BM metastasis as opposed to those without BM metastasis (1.57 vs. 0.76%, P=0.0472).
Conclusion: The tumor immune microenvironment in BM metastasis was skewed toward immunosuppressive state. Further investigations are warranted to understand the involvement of other immune cells that also suppress immune system, such as regulatory T cells and M2 macrophages.
Citation Format: Asaki Saijo, Keiichi Kinowaki, Kazumasa Yamamoto, Shogo Watanabe, Kohji Takemura, Takeshi Yamaguchi, Yuko Tanabe, Koichi Suyama, Hiromu Yano, Yoshihiro Komohara, Yuji Miura. Tumor immune microenvironment of bone marrow metastasis in patients with solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5518.