CD47 Expression in Solid Tumors Correlates with Phagocytic Tumor-Associated Macrophage Gene Signature

CD47 is a “don't eat me” signal that is frequently 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 functionally defined key TAM subsets have been identified: complement C1q C chain positive (C1QC) TAMs, which display pro-phagocytic activity, and secreted phosphoprotein 1 positive (SPP1) TAMs that express pro-angiogenic markers. Here we characterize CD47 expression and its relationship with tumor macrophages in solid tumor samples. Overall design: Resectable tumors from patients with head and neck squamous cell carcinoma (HNSCC), breast cancer (BC), and colorectal cancer (CRC) were profiled by RNA sequencing. FFPE samples were procured from commercial sources. Whole slide FFPE samples of tumor biopsies were used without further microdissection. RNA was extracted from all samples and subjected to mRNA sequencing

CD47是一种“别吃我”信号，常在肿瘤细胞中高表达，以逃避免疫系统中肿瘤相关巨噬细胞（Tumor Associated Macrophages, TAM）的吞噬作用。靶向CD47的在研药物（如马格妥单抗（magrolimab））旨在介导TAM对肿瘤细胞的吞噬作用。此前已有研究通过功能特性鉴定出两类关键的TAM亚群：补体C1q C链阳性（Complement C1q C Chain Positive, C1QC）TAM，其具有促吞噬活性；以及分泌型磷蛋白1阳性（Secreted Phosphoprotein 1 Positive, SPP1）TAM，该亚群表达促血管生成标志物。本研究对实体瘤样本中的CD47表达情况及其与肿瘤巨噬细胞的关联进行了表征。实验设计：收集头颈部鳞状细胞癌（Head and Neck Squamous Cell Carcinoma, HNSCC）、乳腺癌（Breast Cancer, BC）及结直肠癌（Colorectal Cancer, CRC）患者的可切除肿瘤样本，开展RNA测序分析。福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）样本购自商业供应商，直接使用肿瘤活检的完整切片FFPE样本，无需额外进行显微切割。提取所有样本的总RNA后，进行mRNA测序。