We conducted spatial immune tumor microenvironment (iTME) profiling using formalin-fixed paraffin-embedded (FFPE) samples of 25 KRAS-mutated non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs), including 12 responders and 13 non-responders. An eleven-marker panel (CD3, CD4, CD8, FOXP3, CD68, arginase-1, CD33, HLA-DR, pan-keratin (PanCK), PD-1, and PD-L1) was used to study the tumor and immune cell compositions. Spatial features at single cell level with cellular neighborhoods and fractal analysis were determined. Spatial features and different subgroups of CD68 cells and FOXP3 cells being associated with response or resistance to ICIs were also identified. In particular, CD68 cells, CD33 and FOXP3 cells were found to be associated with resistance. Interestingly, there was also significant association between non-nuclear expression of FOXP3 being resistant to ICIs. We identified CD68 cells in the lung cancer tissues being associated with improved responses, which should be insightful for future studies of tumor immunity.
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http://dx.doi.org/10.1038/s41698-024-00626-6 | DOI Listing |
Mol Ther Methods Clin Dev
December 2024
Research Institute, Children's Hospital of Orange County, Orange, CA, USA.
Mucopolysaccharidosis type I (MPS I) is a metabolic disorder characterized by a deficiency in α-l-iduronidase (IDUA), leading to impaired glycosaminoglycan degradation. Current approved treatments seek to restore IDUA levels via enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). The effectiveness of these treatment strategies in preventing neurodegeneration is limited due to the inability of ERT to penetrate the blood-brain barrier (BBB) and HSCT's limited CNS reconstitution of IDUA levels.
View Article and Find Full Text PDFZhonghua Bing Li Xue Za Zhi
January 2025
Department of Pathology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou450052, China.
To investigate the clinicopathological and molecular genetic characteristics of intracranial mesenchymal tumors with FET::CREB fusion transcript. The clinical and imaging data of 6 cases of intracranial mesenchymal tumors with FET::CREB fusion from December 2018 to December 2023 were collected at the First Affiliated Hospital of Zhengzhou University. Their histological features, immunophenotype and molecular characteristics were analyzed.
View Article and Find Full Text PDFHistiocytosis are caused by pathogenic myeloid cells, and can be classified as Langerhans cell histiocytosis (LCH) and non-LCH. Erdheim-Chester disease (ECD) is a non-LCH, characterized by multi-organ involvement, typical imaging findings, and confirmatory histological studies. A case with multi-organ involvement and histological confirmation is presented.
View Article and Find Full Text PDFJ Clin Exp Hepatol
November 2024
Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen, Germany.
Background: Due to malnutrition and tumor cachexia, body composition (BC) is frequently altered and known to adversely affect short- and long-term results in patients with cholangiocarcinoma (CCA). Here, we explored immune cell populations in the tumor and liver of CCA patients with respect to BC.
Methods: A cohort of 96 patients who underwent surgery for CCA was investigated by multiplexed immunofluorescence (MIF) techniques with computer-based analysis on whole-tissue slide scans to quantify and characterize immune cells in normal liver and tumor regions.
Am J Pathol
January 2025
Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan.
Tumor-infiltrating macrophages (Mϕs), known as tumor-associated macrophages (TAMs), play a crucial role in the tumor microenvironment. Immunohistochemistry (IHC) revealed that intratumoral CD68-positive Mϕs are associated with poor prognosis and clinicopathological factors in patients with hepatocellular carcinoma (HCC). Subsequently, an indirect co-culture system involving HCC cells and peripheral blood-derived Mϕs was developed.
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