T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment-naïve subjects and mice with GBM can harbor AIDS-level CD4 counts, as well as contracted, T cell-deficient lymphoid organs. Missing naïve T cells are instead found sequestered in large numbers in the bone marrow. This phenomenon characterizes not only GBM but a variety of other cancers, although only when tumors are introduced into the intracranial compartment. T cell sequestration is accompanied by tumor-imposed loss of S1P1 from the T cell surface and is reversible upon precluding S1P1 internalization. In murine models of GBM, hindering S1P1 internalization and reversing sequestration licenses T cell-activating therapies that were previously ineffective. Sequestration of T cells in bone marrow is therefore a tumor-adaptive mode of T cell dysfunction, whose reversal may constitute a promising immunotherapeutic adjunct.

中文翻译：

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在胶质母细胞瘤和其他颅内肿瘤的情况下，隔离骨髓中的T细胞。

T细胞功能障碍有助于癌症患者的肿瘤免疫逃逸，在胶质母细胞瘤（GBM）中尤其严重。除其他缺陷外，T细胞淋巴细胞减少是特征性疾病，但通常归因于治疗。我们发现，即使是未接受过治疗的GBM受试者和小鼠也可以携带AIDS级CD4计数以及收缩的T细胞缺陷型淋巴器官。相反，缺失的幼稚T细胞被大量隔离在骨髓中。这种现象不仅是GBM的特征，而且是其他多种癌症的特征，尽管只有在将肿瘤引入颅内腔时才表现出来。T细胞隔离伴随着肿瘤从T细胞表面造成的S1P1损失，并且在排除S1P1内在化后是可逆的。在GBM的鼠模型中，阻碍了S1P1的内在化并逆转了螯合许可证，而以前无效的T细胞活化疗法。因此，骨髓中T细胞的隔离是T细胞功能障碍的一种肿瘤适应模式，其逆转可能构成有希望的免疫治疗辅助剂。