Innate αß T Cells Mediate Antitumor Immunity by Orchestrating Immunogenic Macrophage Programming.

Unconventional T-lymphocyte populations are emerging as important regulators of tumor immunity. Despite this, the role of TCRαß+CD4-CD8-NK1.1- innate αß T cells (iαßT) in pancreatic ductal adenocarcinoma (PDA) has not been explored. We found that iαßTs represent ∼10% of T lymphocytes infiltrating PDA in mice and humans. Intratumoral iαßTs express a distinct T-cell receptor repertoire and profoundly immunogenic phenotype compared with their peripheral counterparts and conventional lymphocytes. iαßTs comprised ∼75% of the total intratumoral IL17+ cells. Moreover, iαßT-cell adoptive transfer is protective in both murine models of PDA and human organotypic systems. We show that iαßT cells induce a CCR5-dependent immunogenic macrophage reprogramming, thereby enabling marked CD4+ and CD8+ T-cell expansion/activation and tumor protection. Collectively, iαßTs govern fundamental intratumoral cross-talk between innate and adaptive immune populations and are attractive therapeutic targets. SIGNIFICANCE: We found that iαßTs are a profoundly activated T-cell subset in PDA that slow tumor growth in murine and human models of disease. iαßTs induce a CCR5-dependent immunogenic tumor-associated macrophage program, T-cell activation and expansion, and should be considered as novel targets for immunotherapy.See related commentary by Banerjee et al., p. 1164.This article is highlighted in the In This Issue feature, p. 1143.

Inferior gluteal and other nerves associated with sacrospinous ligament: a cadaver study.

BACKGROUND: Reported rates of gluteal pain after sacrospinous ligament fixation range from 12-55% in the immediate postoperative period and from 4-15% 4-6 weeks postoperatively. The source of gluteal pain often is attributed to injury to the nerve to levator ani or pudendal nerve. The inferior gluteal nerve and other sacral nerve branches have not been examined thoroughly as potential sources of gluteal pain. OBJECTIVES: The purpose of this study was to further characterize anatomy of the inferior gluteal nerve and other nerves that are associated with the sacrospinous ligament from a combined gluteal and pelvic approach and to correlate findings to sacrospinous ligament fixation. STUDY DESIGN: Dissections were performed in female cadavers that had not been embalmed with gluteal and pelvic approaches. From a pelvic perspective, the closest structure to the superior border of the sacrospinous ligament midpoint was noted, and the sacral nerves that perforated the ventral surface of coccygeus muscle were examined. From a gluteal perspective, the closest distances from ischial spine to the pudendal, inferior gluteal, posterior femoral cutaneous, and sciatic nerves were measured. In addition, the closest distance from the midpoint of sacrospinous ligament to the inferior gluteal nerve and the origin of this nerve were documented. The thickness and height of the sacrospinous ligament at its midpoint were measured. Sacral nerve branches that coursed between the sacrospinous and sacrotuberous ligaments were assessed from both a pelvic and a gluteal approach. Descriptive statistics were used for data analysis. RESULTS: Fourteen cadavers were examined. From a pelvic perspective, the closest structure to the superior border of sacrospinous ligament at its midpoint was the S3 nerve (median distance, 3 mm; range, 0-11 mm). Branches from S3 and/or S4 perforated the ventral surface of coccygeus muscles in 94% specimens. From a gluteal perspective, the closest structure to ischial spine was the pudendal nerve (median distance, 0 mm; range, 0-9 mm). Median closest distance from inferior gluteal nerve to ischial spine and to the midpoint of sacrospinous ligament was 28.5 mm (range, 6-53 mm) and 31.5 mm (range, 10-47 mm), respectively. The inferior gluteal nerve arose from dorsal surface of combined lumbosacral trunk and S1 nerves in all specimens; a contribution from S2 was noted in 46% of hemipelvises. At its midpoint, the sacrospinous ligament median thickness was 5 mm (range, 2-7 mm), and its median height was 14 mm (range, 3-22 mm). In 85% of specimens, 1 to 3 branches from S3 and/or S4 nerves pierced or coursed ventral to the sacrotuberous ligament and perforated the inferior portion of the gluteus maximus muscle. CONCLUSIONS: Damage to the inferior gluteal nerve during sacrospinous ligament fixation is an unlikely source for postoperative gluteal pain. Rather, branches from S3 and/or S4 that innervate the coccygeus muscles and those coursing between the sacrospinous and sacrotuberous ligaments to supply gluteus maximus muscles are more likely to be implicated. A thorough understanding of the complex anatomy surrounding the sacrospinous ligament, limiting depth of needle penetration into the ligament, and avoiding extension of needle exit or entry point above the upper extent of sacrospinous ligament may reduce nerve entrapment and postoperative gluteal pain.

AIDS Cholangiopathy in an Asymptomatic, Previously Undiagnosed Late-Stage HIV-Positive Patient from Kenya.

AIDS-associated cholangiopathy is a form of biliary tract inflammation with stricture formation seen in AIDS patients who are severely immunosuppressed. It is no longer common in countries in which HAART therapy is widely employed but is still seen in underdeveloped countries. The majority of patients are symptomatic at the time of presentation. Herein, we describe a seventy-four-year-old woman who presented with unilateral leg swelling after a prolonged airplane flight. She was otherwise entirely asymptomatic. Routine laboratory testing was notable for a hypochromic microcytic anemia, slight leukopenia, and mild hypoalbuminemia. Liver enzymes were all elevated. Deep venous thrombosis was confirmed, and a CT scan of the chest disclosed no pulmonary emboli. However, the visualized portion of the abdomen showed dilatation of the common bile and pancreatic ducts. This was confirmed on ultrasonography and MRCP, and no obstructive lesions were noted. An ERCP revealed a dilated common bile duct without filling defects or strictures. A balloon occlusion cholangiogram showed strictures and beading of the intrahepatic ducts. Shortly thereafter, serology for HIV returned positive along with a depressed CD4 cell count, and the patient was diagnosed with AIDS-associated cholangiography.