Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Cancer Res. 2024 Nov 15;84(22):3712-3714. doi: 10.1158/0008-5472.CAN-24-3362.
Tumor-associated microglia and macrophages (TAM) make up the largest immune cell population in the glioblastoma (GBM) tumor microenvironment. Given the heterogeneity and plasticity of TAMs in the GBM tumor microenvironment, understanding the context-dependent cancer cell-TAM symbiotic interaction is crucial for understanding GBM biology and developing effective therapies. In a recent issue of Cell, Kloosterman and colleagues identified a subpopulation of glycoprotein nonmetastatic melanoma protein Bhigh lipid-laden microglia and macrophages (LLM) in GBM. Mesenchymal-like GBM cells help generate the LLM phenotype. Reciprocally, LLMs are epigenetically rewired to recycle myelin and transfer the lipid from myelin to cancer cells, fueling mesenchymal-like GBM progression in a liver X receptor/ABCA1-dependent manner. Together, leveraging LLMs opens new therapeutic possibilities for rewiring the metabolism-mediated tumor-TAM interaction during GBM progression.
肿瘤相关的小胶质细胞和巨噬细胞（TAM）构成了胶质母细胞瘤（GBM）肿瘤微环境中最大的免疫细胞群体。鉴于 GBM 肿瘤微环境中 TAMs 的异质性和可塑性，了解依赖于上下文的癌细胞-TAM 共生相互作用对于理解 GBM 生物学和开发有效的治疗方法至关重要。在最近的一期《Cell》杂志上，Kloosterman 及其同事在 GBM 中鉴定出了一群糖蛋白非转移性黑色素瘤蛋白 Bhig 脂滴富含的小胶质细胞和巨噬细胞（LLM）。间充质样 GBM 细胞有助于产生 LLM 表型。反过来，LLM 被表观遗传重编以回收髓磷脂并将脂质从髓磷脂转移到癌细胞中，以肝 X 受体/ABCA1 依赖的方式促进间充质样 GBM 的进展。总之，利用 LLM 为在 GBM 进展过程中重新布线代谢介导的肿瘤-TAM 相互作用提供了新的治疗可能性。
