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Anti-CTLA-4 generates greater memory response than anti-PD-1 via TCF-1.
Proc Natl Acad Sci U S A
January 2025
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
The effects of T cell differentiation arising from immune checkpoint inhibition targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) on the immunological memory response remain unclear. Our investigation into the effects of anti-CTLA-4 and anti-PD-1 on memory T cell formation in mice reveals that memory T cells generated by anti-CTLA-4 exhibit greater expansion, cytokine production, and antitumor activity than those from anti-PD-1. Notably, anti-CTLA-4 preserves more T cell factor-1 (TCF-1)+ T cells during priming, while anti-PD-1 leads to more thymocyte selection-associated high mobility group box (TOX)+ T cells.
View Article and Find Full Text PDFArticle Synopsis
- - Charon, Pluto's largest moon, has been studied for its composition and changes caused by radiation, but previous spectral data only covered wavelengths below 2.5 μm, leaving some questions unanswered.
- - Recent observations using JWST have detected carbon dioxide (CO) and hydrogen peroxide (HO) on Charon's northern hemisphere, adding to its known chemical components like water ice and ammonia.
- - The presence of HO suggests active processes affecting the water ice surface, while spectral analysis indicates that CO is mainly found in crystalline form, likely originating from subsurface sources and other processes involving hydrocarbons and solar interactions.
Microbial metabolite-guided CAR T cell engineering enhances anti-tumor immunity via epigenetic-metabolic crosstalk.
bioRxiv
September 2024
Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Article Synopsis
- Research shows a correlation between the gut microbiome and the effectiveness of cancer immunotherapy, specifically for CAR T cell patients.
- The study identifies pentanoate, a metabolite from commensal bacteria, as a key factor that enhances patient survival by improving CAR T cell performance in challenging tumor environments.
- Findings suggest that incorporating microbial metabolites like pentanoate into CAR T cell manufacturing can exploit metabolic pathways and epigenetic changes to enhance treatment outcomes.
Broad-spectrum antibiotics disrupt homeostatic efferocytosis.
Nat Metab
September 2024
Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
The clearance of apoptotic cells, termed efferocytosis, is essential for tissue homeostasis and prevention of autoimmunity. Although past studies have elucidated local molecular signals that regulate homeostatic efferocytosis in a tissue, whether signals arising distally also regulate homeostatic efferocytosis remains elusive. Here, we show that large peritoneal macrophage (LPM) display impairs efferocytosis in broad-spectrum antibiotics (ABX)-treated, vancomycin-treated and germ-free mice in vivo, all of which have a depleted gut microbiota.
View Article and Find Full Text PDFLAG-3 sustains TOX expression and regulates the CD94/NKG2-Qa-1b axis to govern exhausted CD8 T cell NK receptor expression and cytotoxicity.
Cell
August 2024
Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology and Immune Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:
Article Synopsis
- Exhausted CD8 T cells in chronic viral infections and cancer express inhibitory receptors (IRs) like PD-1, which can be blocked to reinvigorate T cell function.
- Co-targeting multiple IRs, such as PD-1 and LAG-3, can enhance T cell response and disease control beyond blocking PD-1 alone.
- The study reveals distinct functions of PD-1 and LAG-3 in T cell activity, showing LAG-3's role in T cell durability and in creating a subset of T cells that are more effective at killing cancer or infected cells.
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