胶质母细胞瘤（GBM）是一种高度恶性的脑癌，尽管有标准治疗方法，但预后仍然不佳。本研究旨在探索PTPN6在免疫治疗中对抗GBM的可行性。我们的研究通过对公开可获得的数据集和功能实验的全面分析来评估PTPN6基因表达、预后价值和与胶质瘤相关的免疫特性。我们评估了PTPN6表达对人类GBM样本和小鼠模型中CD8+ T细胞耗竭、免疫抑制和肿瘤生长的影响。我们的研究结果表明，PTPN6过表达在GBM中发挥了一个致癌作用，并且与高级别肿瘤和不利的临床结果有关。在人类GBM样本中，PTPN6上调与免疫抑制形成和CD8+ T细胞功能障碍紧密相关，而在小鼠中，则抑制了CD8+ T细胞的浸润。此外，PTPN6促进了细胞周期进程，抑制了细胞凋亡，并在小鼠中促进了胶质瘤细胞增殖、肿瘤生长和集落形成。我们的研究结果表明，PTPN6是一种有前景的GBM免疫治疗靶点。抑制PTPN6可增强CD8+ T细胞浸润并改善抗肿瘤免疫应答，从而改善GBM患者的临床结果。

Glioblastoma (GBM) is a highly malignant brain cancer with a poor prognosis despite standard treatments. This investigation aimed to explore the feasibility of PTPN6 to combat GBM with immunotherapy. Our study employed a comprehensive analysis of publicly available datasets and functional experiments to assess PTPN6 gene expression, prognostic value, and related immune characteristics in glioma. We evaluated the influence of PTPN6 expression on CD8+ T cell exhaustion, immune suppression, and tumor growth in human GBM samples and mouse models. Our findings demonstrated that PTPN6 overexpression played an oncogenic role in GBM and was associated with advanced tumor grades and unfavorable clinical outcomes. In human GBM samples, PTPN6 upregulation showed a strong association with immunosuppressive formation and CD8+ T cell dysfunction, whereas, in mice, it hindered CD8+ T cell infiltration. Moreover, PTPN6 facilitated cell cycle progression, inhibited apoptosis, and promoted glioma cell proliferation, tumor growth, and colony formation in mice. The outcomes of our study indicate that PTPN6 is a promising immunotherapeutic target for the treatment of GBM. Inhibition of PTPN6 could enhance CD8+ T cell infiltration and improve antitumor immune response, thus leading to better clinical outcomes for GBM patients.