Plasma Cytokine and Chemokine Profiles Predict Efficacy and Toxicity of Anti-CD19 CAR-T Cell Therapy in Large B-Cell LymphomaZeng, Zhang, Wang
et alClin Lymphoma Myeloma Leuk (2025)
Abstract: Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising treatment for large B-cell lymphoma (LBCL); however, durable complete responses are achieved in only 30% to 40% of patients. Additionally, CAR-T therapy is frequently associated with significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).We explored the translational potential of cytokines and chemokines as predictive biomarkers for CAR-T outcomes by analyzing 47 plasma cytokines/chemokines in serial blood samples from 24 LBCL patients undergoing CAR-T therapy. Blood samples were collected at multiple times: prelymphodepletion, day of CAR-T infusion (Day 0), and post-infusion. We investigated the association between cytokine levels and key clinical outcomes using machine learning models, including treatment response at 3 months, CRS, and ICANS.Higher day 0 IL-7, day 7 IL-21, and day 0 CCL8 levels correlated with improved remission rates. Conversely, elevated CRS risk was linked to higher day 0 CCL17 and day 3 CCL13, IL-6, and IFN-γ levels. ICANS development was associated with increased day 0 TGF-β1, and day 3 IL-5 and IL-7 levels, while lower day 0 CCL19 and day 3 VIP levels were inversely related to ICANS risk. Additionally, patients who received higher-intensity lymphodepletion had elevated day 0 CCL2 and IL-15 levels.These findings highlight the role of plasma cytokines and chemokines as biomarkers for predicting both the therapeutic efficacy and toxicity of CART, with the potential to guide more personalized, safer, and effective immunotherapies for B cell lymphoma.Copyright © 2025. Published by Elsevier Inc.
IL-7Rα signaling in regulatory T cells of adipose tissue is essential for systemic glucose homeostasisTani-Ichi, Abe, Miyachi
et alJ Immunol (2025)
Abstract: Regulatory T cells (Tregs) mediate tissue homeostasis and repair. The function of the interleukin-7 receptor α (IL-7Rα) in nonlymphoid tissue Tregs is still unknown, although low expression of IL-7Rα is a widely accepted marker for Tregs. Here, we show that IL-33R (ST2)-expressing Tregs in the visceral adipose tissue (VAT) express the IL-7Rα at high levels. Treg-specific IL-7Rα-deficient mice exhibited reduced adipose ST2+ Tregs and impaired glucose tolerance, whereas IL-7Rα was dispensable for Tregs in lymphoid tissues. Mice deficient in thymic stromal lymphopoietin (TSLP), an additional ligand for IL-7Rα, displayed a modest decrease in adipose ST2+ Tregs and a reduced accumulation of adipose eosinophils, accompanied by slightly impaired glucose tolerance. In the VAT, mesothelial cells expressed IL-7, whereas adipose stem cells and folate receptor β-expressing tissue-resident macrophages expressed TSLP. Thus, this study indicates the significance of IL-7Rα signaling in the maintenance of VAT Tregs and glucose homeostasis, revealing a novel role for IL-7 and TSLP in immunometabolism.© The Author(s) 2025. Published by Oxford University Press on behalf of The American Association of Immunologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
JAK inhibition and axial spondyloarthritis: new steps on the path to understanding pathophysiologyCiccia, McGonagle, Thomas
et alFront Immunol (2025) 16, 1488357
Abstract: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that predominantly affects the sacroiliac joints and spine. Tumor necrosis factor (TNF) and interleukin (IL)-17A are key cytokines in disease pathogenesis and are established axSpA treatment targets. Recently, axSpA treatment options have been complemented by Janus kinase inhibitors (JAKi), which inhibit various cytokines without directly impacting TNF or IL-17 signaling. The effect of JAKi on axSpA remains under investigation: besides a JAK2-mediated (and potentially tyrosine kinase 2 [TYK2]-mediated) effect on the IL-23/IL-17 axis, emerging evidence suggests γδ T cells, type 3 innate lymphoid cells, and mucosa-associated invariant T cells, which are dependent on IL-7 and/or IL-15 and thus on JAK1, are strongly inhibited by JAKi used to treat axSpA. This review summarizes potential effects of JAKi on axSpA and shows evidence from pre-clinical/clinical studies. Greater understanding of the mechanisms of action of available treatments may improve knowledge of axSpA and pave the road for future therapies.Copyright © 2025 Ciccia, McGonagle, Thomas, Marzo-Ortega, Martin, Yndestad and Volkov.
Circulatory CCL2 distinguishes Duchenne muscular dystrophy dogsPérez-López, Burke, Hakim
et alDis Model Mech (2025) 18 (3)
Abstract: To establish a minimally invasive approach to studying body-wide muscle inflammation in the canine Duchenne muscular dystrophy (DMD) model, we evaluated 13 cytokines/chemokines in frozen sera from 90 affected (239 sera) and 73 normal (189 sera) dogs (0.00 to 45.2 months of age). Linear mixed-effects model analysis suggested that ten cytokines/chemokines were significantly elevated in affected dogs, including interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, C-C motif chemokine ligand 2 (CCL2), C-X-C motif chemokine ligand 1 (CXCL1) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Further, cytokine/chemokine elevation coincided with the onset of muscle disease. Importantly, only CCL2 showed consistent changes at all ages, with the most pronounced increase occurring between 3 and 9 months. To study the effects of sample storage and type, we compared fresh versus frozen, and serum versus plasma, samples from the same dog. Similar readings were often obtained in fresh and frozen sera. Although plasma readings were significantly lower for many cytokines/chemokines, this did not compromise the robustness of CCL2 as a biomarker. Our study establishes a baseline for using circulatory cytokines/chemokines as biomarkers in canine DMD studies.© 2025. Published by The Company of Biologists.
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