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Background: Osteosarcoma (OS) patients have a poor response to immunotherapy due to the sheer complexity of the immune system and the nuances of the tumor-immune microenvironment. . To gain insights into the immune heterogeneity of OS, we identified robust clusters of patients based on the immune gene expression profiles of OS patients in the TARGET database and assessed their reproducibility in an independent cohort collected from the GEO database. The association of comprehensive molecular characterization with reproducible immune subtypes was accessed with ANOVA. Furthermore, we visualized the distribution of individual patients in a tree structure by the graph structure learning-based dimensionality reduction algorithm.
Results: We found that 87 OS samples can be divided into 5 immune subtypes, and each of them was associated with distinct clinical outcomes. The immune subtypes also demonstrated widely different patterns in tumor genetic aberrations, tumor-infiltrating, immune cell composition, and cytokine profiles. The immune landscape of OS uncovered the significant intracluster heterogeneity within each subtype and depicted a continuous immune spectrum across patients.
Conclusion: The established five immune subtypes in our study suggested immune heterogeneity in OS patients and may provide optimal individual immunotherapy for patients exhibiting OS.
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http://dx.doi.org/10.1155/2021/6649412 | DOI Listing |
Autophagy
September 2025
Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Immune checkpoint inhibitors (ICIs) can re-active the immune response and induce a complete response in mismatch repair-deficient and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, most CRCs exhibit proficient mismatch repair and microsatellite stable (pMMR/MSS) phenotypes with limited immunotherapy response because of sparse intratumoral CD8 T-lymphocyte infiltration. Cellular senescence has been reported to involve immune cell infiltration through a senescence-associated secretory phenotype (SASP).
View Article and Find Full Text PDFAdv Pharm Bull
July 2025
Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Tehran, Iran.
Liver fibrosis (LF) is a pathological condition resulting from a chronic inflammatory response to multiple etiological factors, including viral infections, excessive alcohol consumption, and metabolic disorders. The important role of macrophages in this process, especially the M2 subtype, has attracted attention as a potential target for macrophage-based immunotherapy. M2 macrophages have anti-inflammatory and reparative properties that enable them to modulate the immune response and facilitate repairing damaged tissues.
View Article and Find Full Text PDFImmunol Res
September 2025
Clinical Medical Research Center, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
The tumor microenvironment (TME) is a complex system composed of the extracellular matrix (ECM) and various cell types, with collagen being one of its core components. Collagen heterogeneity profoundly influences tumor progression and the remodeling of the immune microenvironment by regulating tumor cell behavior, signaling pathways, and immune evasion in TME. Different subtypes of collagen significantly affect tumor growth, metastasis, and therapeutic responses by modulating the infiltration and function of immune cells.
View Article and Find Full Text PDFNeurology
October 2025
Department of Neurology, Mayo Clinic, Rochester, MN.
Monoclonal gammopathy-associated myopathies (MGAMs) are rare yet treatable myopathies that occur in association with monoclonal gammopathies. These myopathies include light chain (AL) amyloidosis myopathy, sporadic late-onset nemaline myopathy (SLONM), scleromyxedema with associated myopathy, and newly reported monoclonal gammopathy-associated glycogen storage myopathy (MGGSM), including the vacuolar myopathy with monoclonal gammopathy and stiffness. All these 4 distinct subtypes of MGAMs typically present in patients aged 40 or older, frequently with a subacute onset of rapidly progressive proximal and axial muscle weakness.
View Article and Find Full Text PDFJCO Clin Cancer Inform
August 2025
Telperian, Austin, TX.
Purpose: Lymphocytes play critical roles in cancer immunity and tumor surveillance. Radiation-induced lymphopenia (RIL) is a common side effect observed in patients with cancer undergoing chemoradiation therapy (CRT), leading to impaired immunity and worse clinical outcomes. Although proton beam therapy (PBT) has been suggested to reduce RIL risk compared with intensity-modulated radiation therapy (IMRT), this study used Bayesian counterfactual machine learning to identify distinct patient profiles and inform personalized radiation modality choice.
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