CD47 expression in solid tumors correlates with phagocytic tumor-associated macrophage gene signature

作者：Nicholas van Buuren, Mengshu Xu, Qiu Zhang, Juana P. Correa, Shiva Zaboli, Azadeh Madjidi, Christina Moon, Szu-Wen Liu, Ruidong Li, Kai‐Hui Sun, Shahed Iqbal, Abhishek Aggarwal, Min Wang, Li Li, Jared Odegard, Kelli L. Boyd · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1699237 · 被引用次数：2 · 研究领域：Phagocytosis and Immune Regulation、Immunotherapy and Immune Responses、Immune cells in cancer

Background: CD47 is a "don't eat me" signal that is overexpressed in tumors to evade phagocytosis by tumor associated macrophages (TAM). Investigational agents targeting CD47, such as magrolimab, aim to induce phagocytosis of tumor cells by TAMs. Previously, two key TAM subsets have been identified: C1QC TAMs, which display pro-phagocytic activity, and SPP1 TAMs that express pro-angiogenic markers. We characterize CD47 expression and its relationship with tumor macrophages in solid tumor samples. Patients and methods: Resectable tumors from head and neck squamous cell carcinoma (n=36) (HNSCC), breast cancer (n=37) (BC), and colorectal cancer (n=36) (CRC) were evaluated for CD47 expression by immunohistochemistry (IHC), two multiplex immunofluorescence panels were used to characterize TAM markers and T cell markers. RNA sequencing was also performed. Results: CD47 protein expression was higher on tumor cells compared to stromal cells across tumor indications tested. Although CRC had the lowest prevalence for CD47 expression in primary tumors, we observed a marked increase in CD47 expression in CRC liver metastases. We developed an SPP1 TAM gene signature and validated a C1QC TAM gene signature to estimate TAM abundances from bulk RNA-Seq data. In the TAM mIF analysis, HNSCC had the highest macrophage density of the indications tested. We observed a positive correlation between a higher C1QC: SPP1 TAM ratio and macrophage phenotype and tumor T cell density. C1QC macrophage sign...