Although immunotherapy has revolutionized cancer treatment, many immunogenic tumors remain refractory to treatment. This can be largely attributed to an immunologically “cold” tumor microenvironment characterized by an accumulation of immunosuppressive myeloid cells and exclusion of activated T cells. Here, we demonstrate that genetic ablation or therapeutic inhibition of the myeloid-specific hematopoietic cell kinase (HCK) enables activity of antagonistic anti–programmed cell death protein 1 (anti-PD1), anti-CTLA4, or agonistic anti-CD40 immunotherapies in otherwise refractory tumors and augments response in treatment-susceptible tumors. Mechanistically, HCK ablation reprograms tumor-associated macrophages and dendritic cells toward an inflammatory endotype and enhances CD8 + T cell recruitment and activation when combined with immunotherapy in mice. Meanwhile, therapeutic inhibition of HCK in humanized mice engrafted with patient-derived xenografts counteracts tumor immunosuppression, improves T cell recruitment, and impairs tumor growth. Collectively, our results suggest that therapeutic targeting of HCK activity enhances response to immunotherapy by simultaneously stimulating immune cell activation and inhibiting the immunosuppressive tumor microenvironment.
CONTEXT (BACKGROUND): It is very essential for a surgeon to have the knowledge of pedicle parameters for stabilizing the thoracic vertebra by Transpedicular screw fixation. AIM: To measure the anterior pedicle diameter, posterior pedicle diameter, pedicle diameter at isthmus (minimum pedicle diameter), sagittal pedicle diameter, pedicle length and chord length of all twelve thoracic vertebrae in south Indian population and to determine the length and diameter of the screw for accurate and hazardless surgery. SETTINGS AND DESIGN: A cadaveric study was done in a medical institution. METHODS AND MATERIALS: Study was done on 20 cadaveric specimens of thoracic region of vertebral column. All the thoracic vertebrae (T1-T12) were separated in all 20 specimens, and in total 480 pedicles were studied for anterior pedicle diameter, posterior pedicle diameter, pedicle diameter at isthmus, sagittal pedicle diameter, pedicle length, and chord length and with the help of these statistics the diameter and length of the screw were determined. STATISTICAL ANALYSIS USED: Simple analysis was used. RESULTS: Pedicle diameter at isthmus (minimum diameter) at T1 is 6.98±1.15, which decreases caudally to minimum at T4 (3.90±0.80) then gradually increases caudally to a maximum at T12 (7.88±1.38). Anterior pedicle diameter at T1 is 7.56±1.09 which decreases caudally to minimum value at T5 (5.28±0.92), and again increases caudally reaching maximum value at T12 (9.04±1.63). Posterior pedicle diameter at T1 is (7.74±1.34) which decreases caudally to minimum at T4 (4.70±1.00), and increases caudally to a maximum value at T12 (8.51±1.20). Sagittal diameter at isthmus is gradually increasing from minimum at T1 (8.47±0.87) to maximum at T12 (15.40±2.20). The Chord length is minimum at T1 (31.88±2.67) and gradually increases caudally to a maximum at T12 (45.57±3.86). The Pedicle length is minimum at T1 (4.84±0.85) and increases caudally to a maximum at T8 (6.14±0.99) and again decreases caudally and at T12 Pedicle length is (5.15±0.64). CONCLUSIONS: Spinal surgeons, neurosurgeons or orthopaedic surgeons should have the essential knowledge of pedicle diameter and chord length for selecting the appropriate Transpedicular screw.
During academic dissection for undergraduate students of abdominal region in 55 years old male cadaver we found that two anomalous arterial trunks arising separately from ventral aspect of abdominal aorta which are 12mm apart. The proximal one was gastro-splenico-phrenic trunk, giving right and left inferior phrenic arteries, left gastric artery and splenic artery , whereas distal one was hepato-mesentric trunk branching into common hepatic artery and superior mesenteric artery. The common hepatic artery was passing posterior to the neck of pancreas and anterior to the portal vein. Gastroduodenal artery was arising from left hepatic artery. Left inferior phrenic artery was giving a branch to supply the spleen. The splenic artery was giving a branch to supply the transverse colon. These anomalies are due to variation and ramifications in the development of ventral splanchnic arteries from dorsal aorta. Knowledge of these kinds of variations is very important for surgeons while performing surgeries on upper abdomen, laparoscopic surgeons of hepato-biliary tract, liver transplant surgeons, and interventional radiologists to avoid catastrophes. Therefore we feel presenting this rare case is very significant.
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