CD4 T cell-intrinsic STING signaling controls the differentiation and effector functions of TH1 and TH9 cells.

BACKGROUND: While stimulator of interferon genes (STING) activation in innate immune cells of the tumor microenvironment can result in CD8 T cell-dependent antitumor immunity, whether STING signaling affects CD4 T-cell responses remains elusive. METHODS: Here, we tested whether STING activation modulated the effector functions of CD4 T cells in vivo by analyzing tumor-infiltrating CD4 T cells and evaluating the contribution of the CD4 T cell-derived cytokines in the antitumor activity of the STING ligand 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) in two mouse tumor models. We performed ex vivo experiments to assess the impact of STING activation on CD4 T-cell differentiation and investigate the underlying molecular mechanisms. Finally, we tested whether STING activation enhances TH9 cell antitumor activity against mouse melanoma upon adoptive transfer. RESULTS: We found that activation of STING signaling cell-intrinsically enhances the differentiation and antitumor functions of TH1 and TH9 cells by increasing their respective production of interferon gamma (IFN-γ) and interleukin-9. IRF3 and type I interferon receptors (IFNARs) are required for the STING-driven enhancement of TH1 cell differentiation. However, STING activation favors TH9 cell differentiation independently of the IFNARs/IRF3 pathway but through mammalian target of rapamycin (mTOR) signaling, underscoring that STING activation differentially affects the fate of distinct CD4 T-cell subsets. The therapeutic effect of STING activation relies on TH1 and TH9-derived cytokines, and STING activation enhances the antitumor activity of TH9 cells upon adoptive transfer. CONCLUSION: Our results reveal the STING signaling pathway as a therapeutic target to boost CD4 T-cell effector functions and antitumor immunity.

Pituitary macroadenoma presenting with brow mass and acromegaly.

A 62-year-old woman presented with a brow mass and acromegaly. Biopsy of the lesion showed fibrous dysplasia. Radiologic imaging revealed a pituitary macroadenoma. The patient underwent transsphenoidal pituitary resection and radiation treatment, followed by medicalmanagement of endocrinopathy.

"A to p" screw versus posterolateral plate for posterior malleolus fixation in trimalleolar ankle fractures.

OBJECTIVES: To compare radiographic and clinical midterm outcomes of posterior malleolar fractures treated with posterior buttress plating versus anterior to posterior lag screw fixation. DESIGN: Retrospective case series. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS: Between January 2002 and December 2010, patients with posterior malleolar fractures were identified by Current Procedural Terminology code and their charts reviewed for eligibility. INTERVENTION: Posterior malleolar fixation using either anterior to posterior (AP) lag screws or posterior buttress plating. MAIN OUTCOME MEASUREMENTS: Demographic data, length of follow-up, range of motion, and postoperative Short Musculoskeletal Function Assessment (SMFA) scores were the main outcome measurements. Immediate postoperative radiographs for residual gap/step-off and final follow-up radiographs for the degree of arthritis that developed were evaluated. RESULTS: Thirty-seven patients were eligible for the study, and 27 chose to participate. Sixteen patients underwent posterior buttress plating, and 11 underwent AP screw fixation with mean follow-up times of 54.9 and 32 months, respectively. Demographic data were similar between groups. The posterolateral plating group demonstrated superior postoperative SMFA scores compared with the AP screw group with statistically significant differences in the SMFA bother index (26.7 vs. 9.2, P = 0.03) and trends toward improvement in the mobility (28.3 vs. 12.9, P = 0.08) and functional indices (20.2 vs. 9.4, P = 0.08). There were no significant differences in the range of motion or the development of ankle arthritis over time. CONCLUSIONS: Patients with trimalleolar ankle fractures in whom the posterior malleolus was treated with posterolateral buttress plating had superior clinical outcomes at follow-up compared with those treated with AP screws. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Reproducibility of spinal back-contour measurements taken with raster stereography in adolescent idiopathic scoliosis.

200 children with a mean age of 12.7 years were measured with the Quantec Spinal Image System (QSIS), which uses computerized raster stereography technology. The aim of the study was to assess the intraobserver reproducibility of QSIS metrics in scoliosis patients and to quantify the effect of postural sway on the measurements. Children were randomly assigned to 1 of 2 groups: Group 1 contained 198 subjects, having 3 digitized measurements of 1 scan; Group 2 contained 200 subjects, undergoing 3 separate QSIS scans with 1 measurenent of each scan. Random-effects variance components models were fit to each outcome variable of interest (subject, scan or measurement) separately for the single scan dataset and the 3 scan dataset. They revealed that data from Group 2 contained greater reliability than data from Group 1 (reliability > or = 80%). The reliability of these parameters was perfect if one performed 3 scans and 3 measurements per scan. Results demonstrate that the QSIS with 3 scans and 1 measurement yields reproducible data from mild idiopathic scoliosis patients and that postural sway has minimal effect on data reproducibility.