Peripheral blood-derived, γ9δ2 t cell-enriched cell lines from glioblastoma multiforme patients exert anti-tumoral effects in vitro.

The goal of this work was to assess the potential of T cells expressing Vγ9Vδ2+ T cell receptors (TCR, γ9δ2T cells) present in peripheral blood (PB) m ononuclear cells (MC, PBMC) of glioblastoma multiforme (GBM) patients to act as anti-tumoral agents. We found that γ9δ2T cell levels were decreased in patients' PB relative to a cohort of healthy donors (HD) (respectively 0.52±0.55%, n=16, vs 1.12±0.6%, n=14, p=0.008) but did not significantly correlate with postoperative survival (R=0.6, p=0.063). Importantly, however, the γ9δ2T cells could be expanded in vitro to consist 51±23% of the cultured lymphocytes (98% CD3+). This was achieved after 14 days of culture in medium containing the amino-bisphosphonate (ABP) Zoledronate (Zol) and interleukin (IL)-2, resulting in γ9δ2T cell-enriched lines (gdTCEL) similar to those of HD derived gdTCEL (54±19%). Moreover, gdTCEL from patients and HD mediated cytotoxicity to GBM-derived cell lines (GBMDCL), which was abrogated by immune-magnetic removal of the γ9δ2T cells. Furthermore, low level interferon (IFN) γ secretion was induced by gdTCEL briefly co-cultured with GBMDCL or autologous - tumor-derived cells, which was greatly amplified in the presence of Zol. Importantly, IFNγ secretion was inhibited by mevastatin but enhanced by cross-linking of butyrophilin 3A1 (CD277) on a CD277+ GBMDCL (U251MG) or by pretreatment of GBMDCL with temozolomide (TMZ). Taken together, these data suggest that γ9δ2T cells in PB of GBM patients can give rise to gdTCEL that mediate anti-tumoral activities.

Posterolateral complex knee injuries: magnetic resonance imaging with surgical correlation.

PURPOSE: To describe the magnetic resonance imaging (MRI) findings of injuries of the posterolateral aspect of the knee and to evaluate the diagnostic capabilities of MRI in the assessment of these injuries. MATERIAL AND METHODS: The MRI studies of 14 patients (mean age 33 years) with trauma to the posterolateral aspect of the knee were retrospectively reviewed, and the imaging findings were correlated with those of surgery. RESULTS: In all patients, MRI showed an intact iliotibial (ITB) band. MRI showed injury to the biceps tendon in 11 (79%), the gastrocnemius tendon in 1 (7%)), the popliteus tendon in 5 (36%), and the lateral collateral ligament (LCL) in 14 (100%) patients. Tear of the anterior cruciate ligament (ACL) was seen in 11 (79%) patients and tear of the posterior cruciate ligament (PCL) in 4 (29%) patients. With routine MRI, visualization of the popliteofibular or fabellofibular ligaments was incomplete. On MRI, the lateral meniscus and the medial meniscus were torn with equal frequency (n = 4; 29%). Osteochondral defects were seen in 5 (36%) cases and joint effusion in all 14 (100%) cases on MRI. Using surgical findings as the standard for diagnosis, MRI proved 86% accurate in the detection of injury to the ITB band, the biceps tendon (93%), the gastrocnemius tendon (100%), the popliteus tendon (86%), the LCL (100%), the ACL (79%), the PCL (86%), the lateral meniscus (90%), the medial meniscus (82%), and the osteochondral structures (79%). Surgical correlation confirmed the MRI findings of joint effusion in all cases. CONCLUSION: MRI is well suited for demonstrating the presence and extent of injuries of the major structures of the posterolateral complex of the knee, allowing characterization of the severity of injury.