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Unresectable recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has a very poor prognosis. Soluble immune checkpoints (sICs) are circulating proteins that result from the alternative splicing of membrane proteins and can modulate the immune response to cancer cells. The aim of our pilot study was to determine the possible role of a comprehensive evaluation of sICs in the classification of prognosis and response to treatment in patients with advanced disease. We evaluated several sICs (CD137, CTLA-4, PD-1, PD-L1, PD-L2, TIM3, LAG3, GITR, HVEM, BTLA, IDO, CD80, CD27, and CD28) from peripheral blood at baseline and investigated the association with clinical characteristics and outcomes. A high baseline soluble LAG3 (sLAG3 > 377 pg/mL) resulted in an association with poor PFS and OS ( = 0.047 and = 0.003, respectively). Moreover, sLAG3 emerged as an independent prognostic factor using an MVA ( = 0.005). The evaluation of sICs, in particular sLAG3, may be relevant for identifying patients with worse prognoses, or resistance to treatments, and may lead to the development of novel targeted strategies.
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http://dx.doi.org/10.3390/jpm11070651 | DOI Listing |
J Transl Med
August 2025
Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
Background: The treatment of Cutaneous Squamous Cell Carcinoma (CSCC) has undergone significant changes with the introduction of Immune Checkpoint Inhibitors (ICIs). While promising results have been observed, their efficacy remains limited to a subset of patients. Soluble immune checkpoint molecules, Interferon-gamma (IFN-γ), and cell-free DNA (cfDNA) could serve as potential biomarkers, particularly in ICI-based therapies.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany.
Background: Immune checkpoint inhibitors (ICIs) have become an integral part of cancer therapy, but only a minority of patients experience durable responsiveness. Response rates vary greatly and are often unpredictable, highlighting the urgent need for predictive biomarkers to guide treatment decisions.
Methods: We investigated immune- and tumor-specific expression and secretion profiles in peripheral blood and tumor samples derived from patients with head and neck squamous cell carcinoma (HNSCC).
Brain
August 2025
Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44801, Bochum, Germany.
Collapse of self-tolerance toward peripheral nervous system antigens initiates chronic inflammatory demyelinating polyneuropathy. This breakdown likely recurs, driving disease onset and flare-ups, providing a window to predict progression before symptoms worsen, yet the mechanisms behind self-tolerance maintenance or disruption remain underexplored. Using a transgenic mouse model with Schwann cell-restricted ovalbumin expression and adoptive transfer of ovalbumin reactive CD8 T-cells, we demonstrate that maintenance of immune tolerance to peripheral nervous system antigen is linked to PD1-axis activity.
View Article and Find Full Text PDFCancer Res Commun
August 2025
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska.
Unlabelled: The gut microbiome's role in the pathogenesis of hematologic malignancies is actively being explored; yet studies on chronic lymphocytic leukemia (CLL) are limited. Using the Eμ-TCL1 murine model of CLL, we identify a unique and dysbiotic disease-associated gut microbiome that develops in mice over time. Leukemic mice show an increase in abundance of pathogenic bacteria, specifically members of the Proteobacteria phylum.
View Article and Find Full Text PDFCell Rep Med
July 2025
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address:
Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of nonmelanoma skin cancer, with 2.4 million cases annually and significant mortality. Photodynamic therapy (PDT) is a promising antitumor strategy, and its integration with immunotherapy has garnered attention.
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