Defective CD3zeta chain expression has been reported in T lymphocytes of patients with inflammatory diseases, such as systemic lupus erythematosus or osteoarthritis, and with cancer. In lupus, the absent CD3zeta chain is replaced by the FcRgamma chain, rendering the T cells hyper responsive. However, there are no data on T lymphocytes from patients with cancer. In this study, the presence of the FcRgamma chain and its associated kinase, Syk, was analysed in patients with gastric adenocarcinoma and healthy subjects. Western blot and immunoprecipitation experiments were carried out with total cell or lipid raft extracts from fresh peripheral blood mononuclear cells or T lymphocytes, and Herpesvirus saimiri-derived T-cell lines (of blood or tissue origin). Our results revealed that the absent CD3zeta chain in cancer T lymphocytes was not replaced by FcRgamma either in fresh T cells or T-cell lines, in contrast to lupus T cells. This altered expression of signalling molecules in T lymphocytes of cancer patients, would explain their low proliferative capacity. Our T-cell lines represent tools to unveil the signalling abnormalities of cancer T lymphocytes.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.molimm.2006.10.012 | DOI Listing |
Sci Rep
October 2024
Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life environmental factors on the risk of celiac autoimmunity were investigated in the multicenter TEDDY birth cohort study.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
October 2024
Ludwig Institute for Cancer Research Lausanne, Department of Oncology, University of Lausanne and Lausanne University Hospital, Lausanne 1011, Switzerland.
The ability to remotely control the activity of chimeric antigen receptors (CARs) with small molecules can improve the safety and efficacy of gene-modified T cells. Split ON- or OFF-switch CARs involve the dissociation of tumor-antigen binding from T cell activation (i.e.
View Article and Find Full Text PDFEBioMedicine
November 2024
National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, 28116, Republic of Korea; Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology (UST), Daejeon, 34113, Republic of Korea. Electronic address:
J Investig Med
January 2025
China Regional Research Center, International Center for Genetic Engineering and Biotechnology, Taizhou, Jiangsu, P. R. China.
NKG2D chimeric antigen receptor (CAR)-modified T cells (NKG2D CAR-T cells) have been reported to be preclinically efficient in several tumors, but little is known whether NKG2D CAR-T cells co-expressing IL21 (IL21-NKG2D CAR-T cells) display greater antitumor activity in multiple myeloma (MM). In this study, the lentivirus has been produced for expression of the IL21 sequence linked to the extracellular NKG2D sequence with the signal peptide linked through the CD8α hinge-transmembrane domain to the 4-1BB molecule fused with the CD3-ζ chain signaling domain, and the engineered IL21-NKG2D CAR-T cells and NKG2D CAR-T cells were constructed. The CAR expression on CAR-T cells was assessed by flow cytometry, and the killing effects of CAR-T cells on MM were assessed by the cytotoxicity assay and ELISA assay.
View Article and Find Full Text PDFInt J Mol Sci
August 2024
Department of Hematology and Central Hematological Laboratory, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland.
In this study, we present the design, implementation, and successful use of digital droplet PCR (ddPCR) for the monitoring of chimeric antigen receptor T-cell (CAR-T) expansion in patients with B-cell malignancies treated with different CAR-T products at our clinical center. Initially, we designed a specific and highly sensitive ddPCR assay targeting the junction between the 4-1BB and CD3ζ domains of tisa-cel, normalized with , and validated it using blood samples from the first tisa-cel-treated patient in Switzerland. We further compared this assay with a published qPCR (quantitative real-time PCR) design.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!