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The limited understanding of the prognostic implications of immune checkpoint molecules in osteosarcoma (OS) poses significant challenges for improving patient outcomes. There is a gap in the identification of reliable biomarkers that can predict treatment response and prognosis in OS patients. This study focused on investigating the prognostic value of immune checkpoints, specifically BTN3A1, SIRPA, and TDO2, using data from the TARGET database and clinical follow-up data from our hospitals. By conducting univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses, we identified these immune checkpoints as significant prognostic indicators. A three-immune-checkpoint genetic prognostic risk model was developed, which demonstrated different prognostic implications across different clinical subgroups. Drug sensitivity analysis revealed that BTN3A1, SIRPA, and TDO2 were correlated with the efficacy of several antineoplastic agents, including hydroxyurea and docetaxel. Validation in our clinical cohort highlighted the significant prognostic value of SIRPA, suggesting its potential as a target for immunotherapy. These findings established a framework for using immune checkpoints as prognostic biomarkers, highlighting their important role in enhancing personalized treatment strategies for OS patients.
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http://dx.doi.org/10.1186/s13018-025-06171-7 | DOI Listing |
Best Pract Res Clin Haematol
September 2025
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA; Dana-Farber/Harvard Cancer Center, Harvard Medical School, Boston, USA.
Immunotherapy, including immune checkpoint blockade, CART cells and bispecific antibodies have resulted in dramatic improvements in outcomes for patients with hematological malignancies, demonstrating the unique potency of the immune system in targeting malignant cells. The development of cancer vaccines aims to evoke an activated effector cell population and a memory response to provide long term immune surveillance to protect from relapse. Developing a potent cancer vaccine relies on identifying appropriate antigen targets, enhancing antigen presentation, and overcoming the immune suppressive milieu of the micro-environment.
View Article and Find Full Text PDFCrit Rev Oncol Hematol
September 2025
Unit of Cancer Genetics, Institute of Genetic & Biomedical Research (IRGB), National Research Council (CNR), Traversa La Crucca n. 3, 07100, Sassari, Italy; Immuno-Oncology & Targeted Cancer Biotherapies, University of Sassari, Viale San Pietro 43, 07100, Sassari, Italy. Electronic address: gpalmier
Mutations in the KRAS gene are prominent oncogenic drivers in non-small cell lung cancer (NSCLC), with multiple pathophysiological, clinical and prognostic implications. Although historically considered an "undruggable" target, recent research led to the development of specific KRAS-G12C inhibitors, like sotorasib and adagrasib which are currently approved for clinical use in patients affected by advanced NSCLC. However, the clinical utility of these drugs is often limited by resistance development through several biological mechanisms, including additional KRAS mutations, activation of compensatory pathways and metabolic reprogramming.
View Article and Find Full Text PDFBiomed J
September 2025
Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University. Electronic address:
Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs), chemotherapy, and molecular targeted therapies have improved survival rates, therapeutic resistance remains a major barrier to curative outcomes. Recently, plasminogen activator inhibitor-1 (PAI-1) has been implicated in lung cancer progression and treatment resistance.
View Article and Find Full Text PDFJ Autoimmun
September 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; Cellular Genomics Futures Institute & School of Biomedical Sciences, UNSW Sydney, Australia. Electronic address:
Background: In autoimmune disease it is not understood how self-reactive B cells escape immune tolerance checkpoints to produce pathogenic autoantibodies.
Objective: In patients with demyelinating polyneuropathy caused by IgM autoantibodies against myelin associated glycoprotein (MAG) and the sulphated trisaccharide CD57, we aimed to test the hypothesis that B cells making the autoantibody escaped tolerance by acquiring lymphoma driver somatic mutations.
Methods: Deep single-cell RNA, DNA, flow cytometric and antibody specificity analysis of blood from three patients with MAG neuropathy.
Lung Cancer
August 2025
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou, China; Guangzhou Institute of Respiratory Health, Guangzhou, C
Background: Large cell neuroendocrine carcinoma (LCNEC) represents a rare and unique type of lung tumor with an unfavorable prognosis. It is essential to summarize the treatment modalities and prognosis for inoperable stage III and IV LCNEC, explore the role of frontline immunotherapy, and examine the stratification role of the Lung Immune Prognostic Index (LIPI) and its relationship with the tumor microenvironment (TME).
Methods: This study retrospectively analyzed 160 patients with inoperable lung LCNEC (L-LCNEC) admitted to three hospitals from December 2012 to November 2023.