Corrigendum: Coexpression of HHLA2 and PD-L1 on tumor cells independently predicts the survival of spinal chordoma patients.

[This corrects the article DOI: 10.3389/fimmu.2021.797407.].

Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients.

Background: Immunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients. Methods: Using multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples. Results: Tumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD-1+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival. Conclusion: These data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.

Interleukin-17A Promotes Human Disc Degeneration by Inhibiting Autophagy Through the Activation of the Phosphatidylinositol 3-Kinase/Akt/Bcl2 Signaling Pathway.

BACKGROUND: Previous studies have suggested that interleukin (IL)-17A is a key factor that contributes to intervertebral disc degeneration (IDD), whereas autophagy has been shown to be a protective mechanism in IDD. However, the relationship between IL-17A and autophagy in IDD remains to be fully elucidated. This study sought to evaluate the association between IL-17 and autophagy and the potential mechanism through which IL-17A affects autophagy in IDD. METHODS: Intervertebral disc specimens were collected from 10 patients with lumbar disc herniation. Human degenerated nucleus pulposus (NP) cells were cultured in the presence or absence of IL-17A treatment. Western blot and monodansylcadaverine staining were used to measure autophagy levels in human degenerated NP cells. Subsequently, phosphatidylinositol 3-kinase (PI3K)/Akt/Bcl-2 pathway inhibitors were used to reveal the potential mechanism. RESULTS: IL-17A treatment inhibited the autophagic activity in human NP cells in a time- and dose-dependent manner. Moreover, monodansylcadaverine staining showed that cells treated with IL-17A had significantly fewer changes in their autophagic vacuoles compared with control-treated cells. After IL-17A treatment, expression levels of PI3K, p-Akt, and Bcl-2 in NP cells were significantly increased. Further assays with PI3K/Akt/Bcl-2 inhibitors revealed that IL-17A suppressed autophagy in NP cells by activating the PI3K/Akt/Bcl-2 signaling pathway. CONCLUSIONS: These data suggest that IL-17A promotes IDD by inhibiting autophagy through activation of the PI3K/Akt/Bcl-2 signaling pathway and may offer new insights for targeted therapy of this disease.

Clinical effect evaluation of percutaneous vertebroplasty combined with the spinal external fixator for the treatment of osteoporotic compressive fractures with posterior vertebral defect.

PURPOSE: The purpose of this study is to report a new technique and assess clinical outcome of compressive fractures with posterior vertebral defect treated by percutaneous vertebroplasty combined with the spinal external fixator. METHOD: 80 patients (32 males and 48 females), ranging from 62 to 88 years old with the mean age of 71.5 years, underwent surgery for the compressive fractures with posterior vertebral defect by percutaneous vertebroplasty combined with the spinal external fixator. All patients were diagnosed to have fresh compressive fractures with osteoporosis and posterior vertebral defect shown on roentgenograms, computed tomography scans or magnetic resonance imaging preoperatively. They underwent spinal external fixation firstly to be fixed and restored, then to be carried out percutaneous vertebroplasty. The mean follow-up was 24 months (16-42 months). Spinal canal encroachment, spinal cobb angle and vertebral body height loss were measured to assess clinical outcome before and after surgery, at the final follow-up. The Visual Analogue Scale and Oswestry Disability Index were used for pain and functional assessment. In all cases, preoperative and postoperative radiographs and magnetic resonance imaging were obtained. RESULTS: The average time of surgery was 88 min (75-115 min). The mean blood loss was 10 ml (6-12 ml) during surgery. The anterior height loss of vertebral body decreased significantly from 79.3 ± 11% before surgery to 8.0 ± 5.2% after surgery, and 7.6 ± 6.0% at the final follow-up. The spinal canal encroachment significantly reduced from 19.9 ± 2.6 % preoperatively to 4.0 ± 0.7% postoperatively, 4.1 ± 0.7% at the final follow-up. The Cobb angle was corrected from 25.8 ± 7.9° primarily to 8.2 ± 4.1° postoperatively, 7.8 ± 3.1° at the final follow-up. There were significant differences (p < 0.05) among them before and after the surgery. Postoperative VAS and Oswestry scores were both significantly different from the preoperative and follow-up (p < 0.05). CONCLUSION: The preliminary results are encouraging, showing that the spinal external fixator combined with percutaneous vertebroplasty was a safe and effective method to treat the osteoporotic compressive fractures with posterior vertebral defect.

Establishing a disc degeneration model using computed tomography-guided percutaneous puncture technique in the rabbit.

BACKGROUND: Various animal models have been developed to investigate the complex mechanisms leading to intervertebral disc disorders and to evaluate the different therapeutic options. The needle puncture technique is commonly used to induce intervertebral degeneration in animal models. The present study aimed to establish a rabbit model of intervertebral disc degeneration using a simple, minimally invasive procedure. METHODS AND MATERIALS: The animal model was created in the rabbit using computed tomography-guided percutaneous puncture technology. An 18-gauge needle was used to induce a disc injury with a 5-mm puncture depth. Radiographic, histologic, and biochemical analyses and magnetic resonance imaging were performed to assess the consequent disc degeneration. RESULTS: Significant disc space narrowing was observed as early as 4 wk, and osteophytes were formed at 12 wk after puncture. The magnetic resonance imaging assessment demonstrated a progressive loss of T2-weighted signal intensity at the stabbed discs throughout the 12-wk period. The histologic analysis showed a progressive loss of the normal architecture from 4 wk to the end point. The biochemical assays suggested that the expression of proteoglycan decreased progressively with increasing time. CONCLUSIONS: A simple, but minimally invasive, intervertebral disc degeneration model was established successfully using computed tomography-guided percutaneous puncture technology in the rabbit. The puncture procedure can be performed with minimal damage and handling of the other structures, ensuring a uniform reproducible disc degeneration model.

Evaluation of biocompatibility of a pectin/polyvinyl alcohol composite hydrogel as a new nucleus material.

OBJECTIVE: To evaluate the biocompatibility of a new kind of prosthetic nucleus: a pectin/polyvinyl alcohol composite (CoPP) hydrogel. METHODS: According to Chinese national standard GB/-T16886 documents, the toxicity of the CoPP prosthetic nucleus material was examined by cytotoxicity, sensitization, Ames, mice marrow micronucleus, chromosome aberration test of mammalian cell and implantation tests. RESULTS: Cell growth was similar in the CoPP culture and control groups. No significant difference was found between the CoPP culture and control groups at each time point (P > 0.05). The cell proliferation rate was greater than 100%. In accordance with the relationship between cytotoxicity to proliferation rate, it was confirmed that the cytotoxicity of CoPP was 0 grade. Mice had no allergic reaction when injected with an extract of CoPP. A reverse mutation test with Salmonella typhimurium showed that no significant effect on the number of histidine revertants of TA97, TA98, TA100 and TA102 strains after CoPP was added. The micronucleus rate in bone marrow cells was less than 5%; there was no significant difference compared with the negative control group (P > 0.05). The rate of chromosome aberration was less than 5%; no significant difference was found between the CoPP culture and the control groups. All experimental animal wounds achieved primary healing without exudation, infection or sinus formation. On macroscopic observation, no abscess or hematoma formed at the implantation site. CONCLUSION: The CoPP prosthetic nucleus has good biocompatibility and can potentially be used as an implant material.