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ANXA10 sensitizes microsatellite instability-high colorectal cancer to anti-PD-1 immunotherapy via assembly of HLA-DR dimers by regulating CD74.
Cell Biol Toxicol
January 2025
Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
Background: Microsatellite instability-high (MSI-H) metastatic colorectal cancer (CRC) patients are the dominant population in immune checkpoint blockade treatments, while more than half of them could not benefit from single-agent immunotherapy. We tried to identify the biomarker of MSI-H CRC and explore its role and mechanism in anti-PD-1 treatments. Tumor-specific MHC-II was linked to a better response to anti-PD-1 in MSI-H CRC and CD74 promoted assembly and transport of HLA-DR dimers.
View Article and Find Full Text PDFA signaling molecule from intratumor bacteria promotes trastuzumab resistance in breast cancer cells.
Proc Natl Acad Sci U S A
January 2025
Key Laboratory of Molecular Nanostructure and Nanotechnology, Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Emerging evidence indicates that intratumor bacteria exist as an active and specific tumor component in many tumor types beyond digestive and respiratory tumors. However, the biological impact and responsible molecules of such local bacteria-tumor direct interaction on cancer therapeutic response remain poorly understood. Trastuzumab is among the most commonly used drugs targeting the receptor tyrosine-protein kinase erbB-2 (ErbB2) in breast cancer, but its resistance is inevitable, severely limiting its clinical effectiveness.
View Article and Find Full Text PDFCryoEM structure of an MHC-I/TAPBPR peptide-bound intermediate reveals the mechanism of antigen proofreading.
Proc Natl Acad Sci U S A
January 2025
Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104.
Class I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive.
View Article and Find Full Text PDFBiomarkers.
Alzheimers Dement
December 2024
Huashan Hospital, Fudan University, Shanghai, Shanghai, China.
Background: Previous studies have suggested a correlation between elevated levels of β-microglobulin (B2M) and cognitive impairment. However, the existing evidence is insufficient to establish a conclusive relationship. This study aims to analyse the link of plasma B2M to cerebrospinal fluid (CSF) Alzheimer's Disease (AD) biomarkers, and cognition.
View Article and Find Full Text PDFEnhanced antibody responses in CD19-Cre mice.
Sci Rep
January 2025
Institute of Biomedicine and MediCity Research Laboratories, University of Turku, Turku, Finland.
CD19-Cre is an important and widely used Cre-lox model for B cell-specific genetic manipulation in murine systems. Mice carrying one allele of CD19-Cre are, at the same time, rendered heterozygote for CD19, a crucial coreceptor of the B cell antigen receptor (BCR). As a result, CD19-Cre mice exhibit diminished expression levels of CD19, with potential, yet insufficiently examined, consequences in B cell activation.
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