No abstract

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.

Object Over the past 15 years, vertebroplasty has emerged as a treatment for vertebral compression fractures. This technique, however, does not restore vertebral height and is associated with a high rate of cement leakage. Recently, kyphoplasty was developed in an effort to circumvent this problem. Although its immediate results have been reported, it is unclear whether the benefits endure. Methods Seventy-eight consecutive patients underwent 188 kyphoplasty procedures. The patients responded to Short Form—36 (SF-36) questionnaires, a visual analog scale (VAS) for pain rating, and the Oswestry disability index (ODI) instrument; additionally they underwent detailed neurological and radiographic examinations pre- and postoperatively. The preoperative SF-36, VAS, and ODI scores, the neurological examination results, and the radiographic data were compared with the postoperative findings. Thirteen patients died of disease progression or unrelated illness. Of the surviving patients, complete data were available in 62% (minimum follow-up period 12 months, mean 18 months). Complications included one myocardial infarction and five cases of asymptomatic cement extravasation. No case of neurological deterioration occurred during the follow-up period. Significant improvements in seven measures of the SF-36 inventory as well as on the ODI and VAS were noted early postoperatively, and these persisted throughout the follow-up period, despite a statistically insignificant decline in the measure of general health at last follow-up examination. Conclusions Kyphoplasty is an effective treatment for vertebral compression fractures. The benefits presented in the early postoperative period and persisted at 1 year posttreatment.