Macrophage is an essential part of the tumor immune microenvironment of pancreatic ductal adenocarcinoma. In our study, we explored the CXCR4 + macrophages subset on its prognosis value, immune profile and distinct function in pancreatic cancer progression. Specimens from 102 postoperative pancreatic patients were analyzed by flow cytometry or immune-fluorescence, and the prognostic value of CXCR4 + macrophages infiltration was further determined by Cox regression. In silico analysis on TCGA, ICGC database and single-cell sequencing of pancreatic ductal adenocarcinoma further validated our findings. We found that high CXCR4 + macrophages infiltration was associated with poor overall survival (P < .01) and disease-free survival (P < .05) as an independent factor. CXCR4 + macrophages exhibited an M2 protumor phenotype with high expression of CD206. The function of CXCR4 + macrophages was further analyzed in the murine orthotopic PDAC model with its tumor promotion effect and inhibition of CD8 + T cells. Mechanistic and RNA-seq analysis showed that CXCR4 + macrophages participated in extracellular matrix remodeling procedures and especially secreted SPARC through CXCR4/PI3K/Akt pathway promoting tumor proliferation and migration. Our study reveals that CXCR4 + macrophages infiltration is an indicator of poor prognosis of PDAC and targeting these cells was potentially crucial in immunotherapy of PDAC.
The aim of this study was to reveal the external features of the bronchial artery (BA) system, so as to provide morphological basis for clinic. The BAs in 48 adult cadavers were dissected and analyzed. The number of BAs in 48 cases was 118. The incidence of BA arising from thoracic aorta, right posterior intercostal artery, and right subclavian artery was 69.49, 27.12, and 3.39%, respectively. The origin of BAs in individual specimen might be single, two, or all of them, respectively. According to the different origin and/or origins of BAs, it could be divided into five categories. As for the course of BAs, in this study, all the left BAs arising from thoracic aorta passed forward around the left side of esophagus and then entered left pulmonary hilum; most (n = 15) of the right BAs arising from thoracic aorta passed forward around the left side of esophagus and then entered right pulmonary hilum; a few (n = 8) of the right BAs arising from thoracic passed forward the right side of esophagus and bronchus and then entered right pulmonary hilum. Besides, in our group, the special courses were that right intercostal-bronchial trunk (RICBT) arising from thoracic aorta passed between vertebra and esophagus and gave off BA which curved forward around the right side of esophagus and then entered right pulmonary hilum, common bronchial trunk (CBT) arising from thoracic aorta passed forward around the left side of esophagus laying anterior to bronchus or posterior to bronchus, then dividing into a left and a right BAs entering right and left pulmonary hilum, respectively. In 4 cadavers, the RICBT gave off the radiculomedullary artery and BA in turn, so radiculomedullary artery has the same origin with BA. Of all BAs, the mean diameter of right posterior intercostal artery, CBT, left BA, and right BA was 2.17 ± 0.84, 1.79 ± 0.57, 1.44 ± 0.50, and 1.39 ± 0.38 mm, respectively. The information gained from this study will be of value in clinic application.
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