Recent data have revealed that Ag presentation by immature dendritic cells (imDCs) plays a role in establishing and maintaining T-cell tolerance, but the mechanism remains unclear. PD-L1 and PD-L2, ligands for programmed-death receptor 1 (PD-1), members of the expanding B7 family, were highlighted for their inhibitory role in T-cell responses. Here, we show that blockade of PD-1 ligands on imDCs resulted in enhanced T-cell proliferation, which is perhaps due to the enhancement of IL-2 production from DC-stimulated T cells. PD-1 ligands blockade on mDCs did not show a significant stimulatory effect as markedly as imDCs. The inhibitory effects of PD-1 ligands would be dependent on maturation status of DCs, where attenuated positive costimulatory molecules provided the opportunity for PD-1 ligands to exert their strong capacity. Our data are consistent with the hypothesis that imDCs have an inhibitory bias, and indicate that PD-L1 and PD-L2 contribute to the poor stimulatory capacity of imDCs.
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http://dx.doi.org/10.1016/j.imbio.2007.01.004 | DOI Listing |
JCI Insight
January 2025
Department of Immunology and.
Tumor-associated macrophages (TAMs) are one of the key immunosuppressive components in the tumor microenvironment (TME) and contribute to tumor development, progression, and resistance to cancer immunotherapy. Several reagents targeting TAMs have been tested in preclinical and clinical studies, but they have had limited success. Here, we show that a unique reagent, FF-10101, exhibited a sustained inhibitory effect against colony-stimulating factor 1 receptor by forming a covalent bond and reduced immunosuppressive TAMs in the TME, which led to strong antitumor immunity.
View Article and Find Full Text PDFACS Catal
January 2025
Institute of Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zurich, Vladimir-Prelog-Weg, 1, 8093 Zurich, Switzerland.
Buchwald-Hartwig (BH) aminations are crucial for synthesizing arylamine motifs in numerous bioactive molecules and fine chemicals. While homogeneous palladium complexes can be effective catalysts, their high costs and environmental impact motivate the search for alternative approaches. Heterogeneous palladium single-atom catalysts (SAC) offer promising recoverable alternatives in C-C cross-couplings.
View Article and Find Full Text PDFBMC Cancer
January 2025
Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China.
Background: Triple-negative breast cancer (TNBC) is among the most aggressive forms of breast cancer, characterized by a dismal prognosis. In the absence of drug-targetable receptors, chemotherapy remains the sole systemic treatment alternative. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors (ICIs) that target programmed death 1/programmed death ligand 1 (PD-1/PD-L1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4), have provided renewed optimism for the treatment of patients with TNBC.
View Article and Find Full Text PDFNature
January 2025
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
T cell exhaustion limits effector T cell function in chronic infection and tumors. The development of these hypofunctional T cells and of their precursors was considered to require stimulatory conditions met only upon persisting exposure to antigen and inflammation. In sharp contrast, we found similar T cell populations in the early phase of acute infections.
View Article and Find Full Text PDFCochrane Database Syst Rev
January 2025
Saúde Baseada em Evidências, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Background: Glioblastoma multiforme (GBM) is the most common and aggressive adult glioma (16-month median survival). Its immunosuppressive microenvironment limits the efficacy of immune checkpoint inhibitors (ICIs).
Objectives: To assess the effects of the ICIs antibodies anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) in treating adults with diffuse glioma.
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