B cells and energy metabolism in HER2-positive DCIS: insights into breast cancer progression from spatial-omics analysesBergholtz, Norum, Lien
et alBreast Cancer Res (2025) 27 (1), 44
Abstract: During breast tumor progression, the transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step with large implications for prognosis. However, the mechanisms of invasion are still largely unknown. At the DCIS stage, there is an over-representation of HER2-positive lesions compared with invasive breast cancer. In this study, we investigated the associations between gene expression profiles in cancer cells and the immune microenvironment of HER2-positive DCIS and invasive breast tumors with concurrent DCIS using spatial transcriptomics. We found distinctly more B cells in the vicinity of DCIS ducts than in invasive tumor areas. There was higher expression of genes involved in energy metabolism in DCIS cancer cells than in invasive cancer cells and a positive correlation between expression of metabolic genes and B-cell abundance in DCIS. In contrast were processes related to epithelial to mesenchymal transition negatively correlated with B-cell abundance in DCIS. We also found significant correlation between expression of the B-cell-attracting chemokines CCL19, CCL21 and CXCL13 in stromal cells and B cell abundance in DCIS. This study indicates that B cells may play a protective role in the progression of HER2-positive DCIS to invasive breast cancer and that increased metabolic activity in intraductal cancer cells in combination with chemokines produced by stromal cells may influence the immune microenvironment of DCIS. These findings have implications for understanding HER2-positive breast cancer progression.© 2025. The Author(s).
Diffuse large B cell lymphoma in rheumatoid arthritis patients is associated with elevated B-cell driving factors including CXCL13Euler, Hellbacher, Klint
et alClin Immunol (2025) 275, 110476
Abstract: Patients with rheumatoid arthritis (RA) are at increased risk of diffuse large B cell lymphoma (DLBCL) compared to the general population. Here, we explored the inflammatory profiles in the blood of RA patients who had developed DLBCL. RA-DLBCL patients had significantly higher levels of the pro-inflammatory markers TNF, IL-8, CXCL9, APRIL, and particularly CXCL13 (median 796 vs. 206 pg/mL, p = 0.001), compared to RA controls. By including an extensive autoantibody panel of rheumatoid factor, IgG anti-CCP2, anti-citrullinated protein antibodies (ACPA) fine-specificities, and other anti-modified protein antibodies, all RA-DLBCL patients were autoantibody seropositive. Yet, RA-DLBCL patients did not display significantly different autoantibody signatures compared to RA controls. The levels of immunoglobulin free light chains and C-reactive protein were similar in RA-DLBCL patients and RA controls. In conclusion, RA-DLBCL patients exhibit pro-inflammatory signatures with elevated markers that are important for B cells and may contribute to enhanced B-cell activation and promote lymphoma development.Copyright © 2024. Published by Elsevier Inc.
Neoadjuvant immune checkpoint therapy: Enabling insights into fundamental human immunology and clinical benefitPauken, Alhalabi, Goswami
et alCancer Cell (2025)
Abstract: While immune checkpoint therapy (ICT) has revolutionized cancer treatment, most patients with advanced disease fail to achieve durable benefit. To address this challenge, it is essential to integrate mechanistic research with clinical studies to: (1) understand response mechanisms, (2) identify patient-specific resistance pathways, (3) develop biomarkers for patient selection, and (4) design novel therapies to overcome resistance. We propose that incorporating "direct-in-patient" studies into clinical trials is crucial for bridging the gap between fundamental science and clinical oncology. In this review, we first highlight recent clinical success of ICT in the neoadjuvant setting, where treatment is given in earlier disease stages to improve outcomes. We then explore how neoadjuvant clinical trials could be utilized to drive mechanistic laboratory-based investigations. Finally, we discuss novel scientific concepts that will potentially aid in overcoming resistance to ICT, which will require future clinical trials to understand their impact on human immune responses.Copyright © 2025 Elsevier Inc. All rights reserved.
CD206 and dust particles are prognostic biomarkers of progressive fibrosing interstitial lung disease associated with air pollutant exposureKadushkin, Yudina, Lukashevich
et alSci Rep (2025) 15 (1), 9669
Abstract: Current management strategies for progressive fibrosing interstitial lung disease (PF-ILD) and non-PF-ILD differ significantly, underscoring the need for early identification of PF-ILD patients. We analyzed the expression of macrophage markers and the number of dust particles (DP) in lung tissue, as well as complete blood count and blood chemistry tests to identify biomarkers of PF-ILD, and examined the effect of certain pollutants on these biomarkers. Lung biopsies were collected from 73 non-PF-ILD patients and 36 PF-ILD patients. DP were quantified in alveolar wall cells (DP-aw) and desquamated epithelial cells (DP-desq) using polarizing light microscopy. Expression of CD206, transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), C-X-C motif ligand 13 (CXCL13), fibroblast growth factor 2 (FGF-2), tumor necrosis factor α (TNFα), and interleukin 1β (IL-1β) was assessed in lung tissue by immunohistochemistry. The numbers of DP-desq, pulmonary expression of CXCL13, IL-1β and CD206 were higher in ILD patients resided for ≥ 15 days per year in places with 24-hour ambient PM10 level of ≥ 50 µg/m3 compared with ILD patients exposed for < 15 days per year to the similar PM10 concentration. Additionally, CXCL13 expression in lung tissue was higher in smoking ILD patients than in non-smoking ILD patients. Compared with non-PF-ILD patients, PF-ILD patients exhibited higher numbers of DP-aw and DP-desq, as well as increased expression of CD206, CXCL13, IL-1β, TGF-β1, and CTGF in lung tissue. Elevated blood neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios were also observed in PF-ILD patients. These biomarkers were found to be independent predictors of PF-ILD. A regression logistic model incorporating NLR, CD206, and DP-desq predicted PF-ILD with an AUC of 0.847, sensitivity of 84.6%, and specificity of 83.3%. Our findings may be useful in predicting PF-ILD and highlight the need for reducing pollutant emission.© 2025. The Author(s).
膜杰作
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