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Background. Rib head dislocation (RHD) in dystrophic scoliosis of type 1 neurofibromatosis (DS-NF1) is a unique disorder caused by skeletal dystrophy and scoliotic instability. No particular surgical manipulation is mentioned in the literature to instruct the spine surgeons to effectively obtain more migration of the dislocated rib head without resection. The present study aimed to investigate the effectiveness of screw/hook insertion at vertebrae with RHDs on the retraction of penetrated rib head from spinal canal.Methods. 37 neurologically intact patients with DS-NF1 and concomitant 53 RHDs undergoing scoliosis surgery without rib head excision were retrospectively reviewed. We used pre and postoperative whole-spine radiographs to determine the Cobb angle and the vertebral translation (VT), and the CT scans to evaluate the intraspinal rib length (IRL) and rib-vertebral angle (RVA). The dislocated ribs were stratified into two groups according to the presence of screw/hook insertion at vertebrae with RHD: screw/hook group and non-screw/hook group. Results. 37 dislocated ribs with screws/hooks insertion at corresponding vertebrae were assigned into the screw/hook group and the remaining 16 dislocated ribs consisted of the non-screw/hook group. In the screw/hook group, the correction rates of Cobb angle and VT were significantly higher than the non-screw/hook group after surgery (58.7±16.0% vs. 30.9±12.4%, p=0.003; 61.8±18.8% vs. 35.1±16.6%, p=0.001; respectively). Similarly, more correction rates of IRL and RVA were found in the screw/hook group than the non-screw/hook group (63.1±31.3% vs. 30.1±20.7%, p=0.008; 17.6±9.7% vs. 7.2±3.6%, p=0.006; respectively). Multiple linear regression analysis revealed that the correction rates of Cobb angle, VT and RVA contributed significantly to correction of IRL (β=0.389, 0.939 and 1.869, respectively; p=0.019, 0.001 and 0.002, respectively).Conclusion. Screw/hook insertion at dystrophic vertebrae with RHDs contributed significantly to the degree of retraction of penetrated rib head from spinal canal. This effectiveness is mediated by more corrections of VT and RVA.

Background. There was a paucity of valid information on how to discriminate between different patterns of convex coronal imbalance (CCI>3cm) in dystrophic scoliosis secondary to Type I neurofibromatosis (DS-NF1), while aggravated postoperative CCI occurred regularly with the causes being insufficiently investigated. We aimed to develop a new classification of CCI in DS-NF1, and to optimize the coronal rebalancing strategies.Methods. NF1-related scoliosis database was reviewed and different types of CCI were identified, and the outcomes of coronal rebalance were analyzed. Results. Two main CCI patterns were defined: thoracic CCI (Type 1) and thoracolumbar/lumbar CCI (Type 2), and were further subtyped by the compensatory behavior of the upper hemi-curve (straight or curved morphology). The incidence of immediate post-op CCI was 0.0% and 63.6% for Type1 and Type 2 groups, respectively. Mismatch of both translation and inclination correction between the upper and lower hemi-curve was significant in the post-op coronal imbalanced group (△Upper Arc Translation/△Lower Arc Translation: 109.6±60.0% vs. 31.8±34.4%, p=0.008; △Upper Arc Inclination/△Lower Arc Inclination: 89.8±36.6% vs. 33.5±37.3%, p=0.012). Multiple linear regression analysis revealed that △UAT/△LAT significantly correlated with the correction of coronal balance distance (β=-21.567; p=0.018). A surgical rebalancing algorithm was proposed to treat each subtype.Conclusion. Thoracolumbar/lumbar CCI in dystrophic scoliosis was prone to suffer high risk of persistent post-op CCI. Satisfying coronal rebalance should rely on maximal translational correction of lower hemi-curve, while the upper hemi-curve played the role of fine-tuning for coronal realignment rather than radical Cobb correction, straight morphology in particular.

Oncolytic viruses are an excellent platform for developing effective strategies in cancer immunotherapy. Several challenges remain in the use of viro-immunotherapy for cancer, such as the lack of costimulatory signals and negative regulation of immune checkpoints. In this study, we designed a novel adenovirus expressing a soluble fusion protein, programmed cell death protein 1 (PD-1)/CD137L, which contains the extracellular domains of PD-1 and CD137L at each terminus (Ad5-PC). Ad5-PC preserved the costimulatory activity of CD137L and facilitated the persistence of activated CD8(+) T cells. Ad5-PC induced strikingly increased antitumor activity in both ascitic and subcutaneous hepatocellular carcinoma (HCC) tumor models, with 70% and 60% long-term cure rates, respectively. The improved antitumor effect of Ad5-PC was attributed to the sustained high-level lymphocyte activation and interferon (IFN)-γ production in the tumor microenvironment, and was essentially dependent on CD8(+) T cells rather than natural killer (NK) cells. Moreover, Ad5-huPC-expressing human soluble PD-1/CD137L fusion protein was effective in suppressing tumor growth and improving survival in a humanized mouse model. We confirmed that Ad5-PC induced tumor-specific and systematic protection against tumor rechallenges at both in situ and distant sites. Thus, Ad5-PC harnesses several distinct functions to efficiently overcome several major hurdles of viro-immunotherapy.

In recent years, the role of cancer immunotherapy has become increasingly important compared to traditional cancer treatments, including surgery, chemotherapy and radiotherapy. Of note, the clinical successes of immune checkpoint blockade, such as PD-1 and CTLA-4, represent a landmark event in cancer immunotherapy development. Therefore, further exploration of how immune checkpoints are regulated in the tumor microenvironment will provide key insights into checkpoint blockade therapy. In this review, we discuss in details about the regulation of immune checkpoints mediated by immune cells, oncolytic viruses, epigenetics, and gut microbiota and mutual regulation by co-expressed checkpoints. Finally, predictions are made for future personalized cancer immunotherapy based on different checkpoint modulations.