To determine whether monoclonal/oligoclonal T cells are present in abdominal aortic aneurysm (AAA) lesions, we amplified beta-chain T cell receptor (TCR) transcripts from these lesions by the nonpalindromic adaptor (NPA)-polymerase chain reaction (PCR)/V-beta-specific PCR followed by cloning and sequencing. Sequence analysis revealed the presence of substantial proportions of identical beta-chain TCR transcripts in AAA lesions in 9 of 10 patients examined, strongly suggesting the presence of oligoclonal populations of alphabeta TCR+ T cells. We have also shown the presence of oligoclonal populations of gammadelta TCR+ T cells in AAA lesions. Sequence analysis after appropriate PCR amplification and cloning revealed the presence of substantial proportions of identical VgammaI and VgammaII TCR transcripts in 15 of 15 patients examined, and of Vdelta1 and Vdelta2 TCR transcripts in 12 of 12 patients. These clonal expansions were very strong. All these clonal expansions were statistically significant by the binomial distribution. In other studies, we determined that mononuclear cells infiltrating AAA lesions express early- (CD69), intermediate- (CD25, CD38), and late- (CD45RO, HLA class II) activation antigens. These findings suggest that active ongoing inflammation is present in the aortic wall of patients with AAA. These results demonstrate that oligoclonal alphabeta TCR+ and gammadelta TCR+T cells are present in AAA lesions. These oligoclonal T cells have been clonally expanded in vivo in response to yet unidentified antigens. Although the antigenic specificity of these T cells remains to be determined, these T cells may play a significant role in the initiation and/or the propagation of the AAA. It appears that AAA is a specific antigen-driven T cell disease.
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http://dx.doi.org/10.1196/annals.1383.019 | DOI Listing |
Front Oncol
January 2025
Department of Clinical Development, POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company, Indianapolis, IN, United States.
Introduction: SPLASH (NCT04647526) is a multicenter phase III trial evaluating the efficacy and safety of [Lu]Lu-PNT2002 radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC). This study leveraged a lead-in phase to assess tissue dosimetry and evaluate preliminary safety and efficacy, prior to expansion into a randomized phase. Here we report those results.
View Article and Find Full Text PDFTransl Lung Cancer Res
December 2024
Department of Medical Oncology, Assistance Publique - Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière Hospital, Institut Universitaire de Cancérologie, CLIP² Galilée, Paris, France.
Background: Oligoprogression (OP) is common in patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs). This study aims to assess the benefit and the safety profile of ablative radiotherapy (RT) for OP in mNSCLC treated with pembrolizumab in first-line setting.
Methods: We retrospectively analyzed records of all consecutive mNSCLC patients who underwent treatment with pembrolizumab (+/- chemotherapy) in first-line setting and developed an OP treated with ablative RT while continuing pembrolizumab, in a French Hospital from 2019 to 2022.
Sci Rep
January 2025
Department of Nuclear Medicine, TUM University Hospital rechts der Isar, TUM School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany.
Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has improved localization of prostate cancer (PC) lesions in biochemical recurrence (BCR) for salvage radiotherapy (SRT). We conducted a retrospective review of patients undergoing F-rhPSMA-7 or F-flotufolastat (F-rhPSMA-7.3)-PET-guided SRT compared with conventional-SRT (C-SRT) without PET.
View Article and Find Full Text PDFCardiovasc Ther
January 2025
Institute of Cardiovascular Science, Translational Medicine Institute, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
Cysteinyl leukotrienes (LTs) and their receptors are involved in the pathogenesis of abdominal aortic aneurysms (AAAs). However, whether CysLT1 receptor antagonists such as montelukast can influence experimental nondissecting AAA remains unclear. Nondissecting AAAs were induced in C57BL/6J mice by transient aortic luminal infusion of porcine pancreatic elastase (PPE).
View Article and Find Full Text PDFJ Pers Med
December 2024
Department of Radiology, University Hospital Tuebingen, 72076 Tübingen, Germany.
: Current guidelines recommend Cisplatin/Gemcitabine/Durvalumab as first-line treatment for inoperable or recurrent cholangiocarcinoma (CCA). Molecular tumor boards (MTB) have the expertise to support organ-specific tumor boards with evidence-based treatment recommendations for subsequent lines of treatment, based on genomic tumor data and scientific evidence. This study evaluates the adoption of an MTB at a comprehensive cancer center in Germany and whether actionable genetic alterations are associated with specific imaging phenotypes.
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