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In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma ( = 46), Ewing sarcoma ( = 32), alveolar rhabdomyosarcoma ( = 20), embryonal rhabdomyosarcoma ( = 77), synovial sarcoma ( = 22) and desmoplastic small round cell tumors (DSRCT) ( = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described.
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http://dx.doi.org/10.18632/oncotarget.19071 | DOI Listing |
Haematologica
September 2025
Department of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Okayama.
Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder characterized by systemic inflammation and lymphadenopathy. Two major clinical subtypes, idiopathic plasmacytic lymphadenopathy (iMCD-IPL) and iMCD with thrombocytopenia, anasarca, fever, renal dysfunction/reticulin fibrosis, and organomegaly (iMCD-TAFRO), exhibit distinct pathophysiologic mechanisms. While interleukin-6 (IL-6) is known to be elevated in iMCD, the differences in IL-6 production sources between subtypes remain unclear.
View Article and Find Full Text PDFHaematologica
September 2025
Division of Medical Oncology, University Hospital Basel, Basel, Switzerland; Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University and University Hospital Basel, Basel.
We previously used a disease-specific B cell receptor (BCR) point mutation (IGLV3-21R110) for selective targeting of a high-risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor (CAR) T cells. Since CLL is a disease of the elderly and a significant fraction of patients is not able to physically tolerate CAR T cell treatment, we explored bispecific antibodies as an alternative for precision targeting of this tumor mutation. Heterodimeric IgG1-based antibodies consisting of a fragment crystallizable region (Fc) attached to both an anti-IGLV3-21R110 Fab and an anti-CD3 (UCHT1) single chain variable fragment (R110-bsAb) selectively killed cell lines engineered to express high levels of the neoepitope as well as primary CLL cells using healthy donor and CLL patient-derived T cells as effectors.
View Article and Find Full Text PDFMol Cancer Ther
September 2025
Case Western Reserve University School of Medicine, Cleveland, OH, United States.
The estrogen receptor (ER or ERα) remains the primary therapeutic target for luminal breast cancer, with current treatments centered on competitive antagonists, receptor down-regulators, and aromatase inhibitors. Despite these options, resistance frequently emerges, highlighting the need for alternative targeting strategies. We discovered a novel mechanism of ER inhibition that targets the previously unexplored interface between the DNA-binding domain (DBD) and ligand-binding domain (LBD) of the receptor.
View Article and Find Full Text PDFStroke
September 2025
Departments of Radiology and Neurology, Neuroprotection Research Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston (E.L., R.M.P., K.H., E.H.L., E.E.).
Background: Despite promising preclinical results, remote limb ischemic postconditioning efficacy in human stroke treatment remains unclear, with mixed clinical trial outcomes. A potential reason for translational difficulties could be differences in circadian rhythms between nocturnal rodent models and diurnal humans.
Methods: Male C57BL/6J mice were subjected to transient focal cerebral ischemia and then exposed to remote postconditioning during their active or inactive phase and euthanized at 24 hours and 3 days.
Blood Press Monit
September 2025
Baishan Maternal and Child Health and Family Planning Service Center, Baishan City, Jilin Province, China.
Objective: This study investigated the relationship of maternal serum uric acid, cystatin C (CysC), and coagulation indices [international normalized ratio (INR) and fibrinogen (FIB)] during pregnancy with clinical features and prognosis of early-onset pre-eclampsia.
Methods: Patients with pre-eclampsia (n = 133) were retrospectively selected, with clinical features and maternal uric acid, CysC, INR, and FIB levels collected. The relationship between clinical features and maternal uric acid, CysC, INR, and FIB was analyzed by Pearson's and Spearman's analyses.