The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS33) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

神经发生和胶质细胞生成与神经胶质瘤的关联仍不清楚。通过对 26 个神经胶质瘤进行单细胞 RNA 测序分析，我们将其分类为原始少突胶质细胞前体细胞 (pri-OPC) 样肿瘤和放射状胶质细胞 (RG) 样肿瘤，并在公共队列和 TCGA 神经胶质瘤中进行了验证。RG样肿瘤表现出野生型异柠檬酸脱氢酶并倾向于携带EGFR突变，而pri-OPC样肿瘤倾向于携带TP53突变。仅在 pri-OPC 样肿瘤中的肿瘤亚克隆表现出显着下调的MHC-I基因，表明它们具有独特的免疫逃避程序。此外，这两个亚组似乎以不同的方式广泛调节神经胶质瘤浸润淋巴细胞。在神经胶质瘤浸润淋巴细胞中发现了一些在正常免疫细胞中不表达的特定基因。例如，神经胶质/神经胶质瘤干细胞标记物OLIG1/PTPRZ1和 B 细胞特异性受体IGLC2/IGKC分别在 pri-OPC 样和 RG 样神经胶质瘤浸润淋巴细胞中表达。它们的表达与免疫检查点基因（例如LGALS33 ）的表达呈正相关，并且通过Jurkat 细胞中IGKC过表达后LGALS3表达增加所证实，存活率较低。这一发现表明对肿瘤浸润淋巴细胞具有潜在的抑制作用，并可能提供一种癌症免疫逃避的新途径。