Coinhibitory receptor blockade is a promising strategy to boost T-cell immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for advanced mechanistic understanding to improve patient outcomes and uncover clinically relevant biomarkers of treatment efficacy. However, the T cell-intrinsic signaling pathways engaged during checkpoint blockade treatment are not well defined, particularly for combination approaches. Using a murine model to study how effector CD8+ T-cell responses to tumors may be enhanced in a tolerizing environment, we identified a critical role for the T-box transcription factor T-bet. Combination blockade of CTLA-4, PD-1, and LAG-3 induced T-bet expression in responding tumor/self-reactive CD8+ T cells. Eradication of established leukemia using this immunotherapy regimen depended on T-bet induction, which was required for IFNγ production and cytotoxicity by tumor-infiltrating T cells, and for efficient trafficking to disseminated tumor sites. These data provide new insight into the success of checkpoint blockade for cancer immunotherapy, revealing T-bet as a key transcriptional regulator of tumor-reactive CD8+ T-cell effector differentiation under otherwise tolerizing conditions.

IMPORTANCE Paramedian forehead flaps are commonly used to reconstruct facial defects caused by skin cancers. Data are lacking on the complications from this procedure, postoperative outcomes, and association of cancer diagnosis with rate of deep venous thrombosis (DVT).OBJECTIVES The primary objective was to determine complication rates after paramedian forehead flap reconstruction for defects resulting from resection of facial cancers; and the secondary objective was to determine patient factors and complications that are associated with readmission.

IMPORTANCEMandible angle fractures can be repaired in a variety of ways, with no consensus on the outcomes of complications and reoperation rates.OBJECTIVES To analyze patient, injury, and surgical factors, including approach to the angle and plating technique, associated with postoperative complications, as well as the rate of reoperation with regard to mandible angle fractures. DESIGN, SETTING, AND PARTICIPANTSRetrospective cohort study analyzing the surgical outcomes of patients with mandible angle fractures between January 1, 2000, and December 31, 2015, who underwent open reduction and internal fixation. Patients were eligible if they were aged 18 years or older, had 3 or less mandible fractures with 1 involving the mandibular angle, and had adequate follow-up data. Patients with comminuted angle fractures, bilateral angle fractures, and multiple surgical approaches were excluded. A total of 135 patients were included in the study. All procedures were conducted at a single, large academic hospital located in an urban setting. MAIN OUTCOMES AND MEASURESMajor complications and reoperation rates. Major complications included in this study were nonunion, malunion, severe malocclusion, severe infection, and exposed hardware. RESULTSOf 135 patients 113 (83.7%) were men; median age was 29 years (range, 18-82 years). Eighty-seven patients (64.4%) underwent the transcervical approach and 48 patients (35.6%) received the transoral approach. Fifteen (17.2%) patients in the transcervical group and 9 (18.8%) patients in the transoral group experienced major complications (difference, 1%; 95% CI, −8% to 10%). Thirteen (14.9%) patients in the transcervical group and 8 (16.7%) patients in the transoral group underwent reoperations (difference, 2%; 95% CI, −13% to 17%). Active smoking had a significant effect on the rate of major complications (odds ratio, 4.04; 95% CI, 1.07 to 15.34; P = .04). CONCLUSIONS AND RELEVANCEDuring repair of noncomminuted mandibular angle fractures, both of the commonly used approaches-transcervical and transoral-can be used during treatment with equal rates of complication and risk of reoperation. For a patient undergoing surgery for mandibular angle fracture, smoking status is more likely to predict surgical outcomes rather than how the surgeon chooses to approach and fixate the fracture.LEVEL OF EVIDENCE 3.

Compared to the single free flap plus locoregional flap, double free flaps are relatively reliable without increasing surgical complications or decreasing flap survival, while only modestly increasing operating times.

Objective Ablations of locally advanced or recurrent head and neck cancer commonly result in large composite orofacial defects. Chimeric flaps represent a unique surgical option for these defects, as they provide diverse tissue types from a single donor site. The purpose of the study was to consolidate the literature on chimeric flaps with regard to postoperative complication rates to help inform surgical decision making. Data Sources The librarian created search strategies with a combination of keywords and controlled vocabulary in Ovid Medline (1946), Embase (1947), Scopus (1823), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrails.gov (1997). Review Methods Candidate articles were independently reviewed by 2 authors familiar with the subject material, and inclusion/exclusion criteria were uniformly applied for article selection. Articles were considered eligible if they included patients who received a single chimeric flap for reconstruction of head and neck defects and if they provided data on complication rates. Results A total of 521 chimeric flaps were included in the study. The major complication rate was 22.6%, while the minor complication rate was 14.0%. There were 7 flap deaths noted in the series. Median operative time and harvest time were 15.0 and 2.5 hours, respectively. Conclusion Chimeric flaps represent a viable option for reconstruction of complex head and neck defects and have complication rates similar to those of double free flaps and single free flaps with locoregional flap while only modestly increasing total operative time.