Hermelo Ismaïl, Virtanen Tuomo, Salonen Iida, Nätkin Reetta, Keitaanniemi Sofia, Tiihonen Aliisa M, Lehtipuro Suvi, Kummola Laura, Raulamo Ella, Nordfors Kristiina, Haapasalo Hannu, Rauhala Minna, Kesseli Juha, Nykter Matti, Haapasalo Joonas, Rautajoki Kirsi
Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.
Tays Cancer Center, Tampere University Hospital and Tampere University, Tampere, Finland.
Cancer Immunol Immunother. 2025 Jan 3;74(2):63. doi: 10.1007/s00262-024-03920-1.
The tumor immune microenvironment (TiME) of human central nervous system (CNS) tumors remains to be comprehensively deciphered. Here, we employed flow cytometry and RNA sequencing analysis for a deep data-driven dissection of a diverse TiME and to uncover noncanonical immune cell types in human CNS tumors by using seven tumors from five patients. Myeloid subsets comprised classical microglia, monocyte-derived macrophages, neutrophils, and two noncanonical myeloid subsets: CD3 myeloids and CD19 myeloids. T lymphocyte subsets included double-negative (CD4 CD8) T cells (DNTs). Noncanonical myeloids and DNTs were explored on independent datasets, suggesting that our DNT phenotype represents γδ T cells. Noncanonical myeloids were validated using orthogonal methods across 73 patients from three independent datasets. While the proportions of classical myeloids agreed with reported malignancy type-associated TiMEs, unexpectedly high lymphocyte frequencies were detected in gliosarcoma, which also showed a unique expression pattern of immune-related genes. Our findings highlight the potential of data-driven approaches in resolving CNS TiME to reveal the mosaic of immune cell types constituting TiME, warranting the need for future studies on the nonclassical immune cell subsets.
人类中枢神经系统（CNS）肿瘤的肿瘤免疫微环境（TiME）仍有待全面解析。在此，我们运用流式细胞术和RNA测序分析，对多样化的TiME进行深入的数据驱动剖析，并通过使用来自5名患者的7种肿瘤，揭示人类CNS肿瘤中非常规免疫细胞类型。髓系亚群包括经典小胶质细胞、单核细胞衍生的巨噬细胞、中性粒细胞以及两种非常规髓系亚群：CD3髓系细胞和CD19髓系细胞。T淋巴细胞亚群包括双阴性（CD4 CD8）T细胞（DNTs）。在独立数据集中对非常规髓系细胞和DNTs进行了探索，表明我们的DNT表型代表γδ T细胞。使用正交方法在来自三个独立数据集的73名患者中验证了非常规髓系细胞。虽然经典髓系细胞的比例与报道的与恶性肿瘤类型相关的TiME一致，但在胶质肉瘤中检测到意外高的淋巴细胞频率，其还显示出免疫相关基因的独特表达模式。我们的研究结果突出了数据驱动方法在解析CNS TiME以揭示构成TiME的免疫细胞类型镶嵌图方面的潜力，这表明未来需要对非经典免疫细胞亚群进行研究。
