Non-classical class Ib (class Ib) genes are found in all jawed vertebrates, including the amphibian Xenopus, which possesses at least 20 distinct Xenopus non-classical class Ib genes (XNCs). As an immune evasion strategy, tumors often downregulate surface expression of classical major histocompatibility complex class Ia molecules. In contrast, cancers commonly express class Ib molecules, presenting an alternative for tumor immune recognition. We characterized a novel XNC, XNC10, functionally similar to CD1d from a class Ia-deficient thymic lymphoid tumor (15/0), which grows aggressively in Xenopus LG-15 cloned animals. To investigate the roles of XNC10 in antitumor immunity, we generated stable 15/0-transfectants with silenced XNC10 mRNA and protein expression. Notably, XNC10 silencing resulted in acute tumor rejection by naturally class Ia-deficient syngeneic tadpoles, with greater potency of rejection in tumors with more efficient XNC10 knockdown. In vivo killing assays shows that the rejection of XNC10-deficient tumors is due to a cell-mediated cytotoxic immune response elicited by the tadpole host. Importantly, priming enhances XNC10-deficient tumor rejection. Flow cytometry reveals that XNC10-deficient tumor rejection is associated with an accumulation of XNC10-restricted invariant T cells and conventional CD8 T cells as well as other leukocytes. Similarly, semisolid tumor grafts in tadpoles also exhibit leukocytes infiltration. These findings suggest that XNC10 allows the 15/0-tumor to escape immune recognition and class Ia-independent cytotoxicity, thus emphasizing the critical roles of class Ibs in tumor immunity.
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http://dx.doi.org/10.1093/carcin/bgu100 | DOI Listing |
Transl Androl Urol
December 2024
Department of Urology, the First Hospital of Lanzhou University, Lanzhou, China.
Background: Bladder urothelial carcinoma (BLCA) is a highly heterogeneous cancer with a wide range of prognoses, ranging from low-grade non-muscle-invasive bladder cancer (NMIBC), which has a good prognosis but a high recurrence rate, to high-grade muscle-invasive bladder cancer (MIBC), which has a poor prognosis. Glycosylation dysregulation plays a significant role in cancer development. Therefore, this study aimed to investigate the role of glycosyltransferases (GT)-related genes in the prognosis of BLCA and to develop a prognostic model based on these genes to predict overall survival (OS) and assess its clinical application.
View Article and Find Full Text PDFMedicine (Baltimore)
November 2024
Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Acute rejection (AR) is a common complication in the early stage after kidney transplantation. Some studies have shown that the occurrence of AR after kidney transplantation may further affect the development of tumors, and both AR and tumor development are related to immune cells and immune genes, so it is particularly important to diagnose the occurrence of AR at an early stage and to analyze the correlation between AR and tumors. In this study, we applied bioinformatics techniques for differential expression analysis and weighted gene co-expression network analysis analysis of AR patients to obtain differentially expressed genes and modular genes significantly associated with AR, respectively, so as to obtain their intersecting genes with immune-related genes; 21 intersecting genes were screened by lasso regression and Boruta algorithm to obtain the genes, and finally, the feature genes that were significantly associated with the dependent variable were further obtained by single-factor and multi-factor logistic regression.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Background: Fibroblast activation protein (FAP)-targeted radioligand therapy, with immunomodulatory effects, has shown efficacy in both preclinical and clinical studies. We recently reported on a novel dimeric FAP-targeting radiopharmaceutical, Ga/Lu-DOTA-2P(FAPI), which demonstrated increased tumor uptake and prolonged retention in various cancers. However, further exploration is required to understand the therapeutic efficacy and underlying mechanisms of combining Ga/Lu-DOTA-2P(FAPI) radioligand therapy with PD-1/PD-L1 immunotherapy.
View Article and Find Full Text PDFJ Clin Med
December 2024
Pharmacy Department, Institut Català Oncologia (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet Llobregat, 08908 Barcelona, Spain.
Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), is actually used to prevent organ transplant rejection and treat metastatic breast, renal, and neuroendocrine cancers. Despite significant pharmacokinetic variability among patients, routine therapeutic drug monitoring (TDM) is not commonly used in oncology. The aim of this multicenter, prospective observational cohort study is to assess the prevalence of everolimus minimum concentration at a steady state (Cminss) falling outside the therapeutic range (10-26.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Gastroenterology, Endocrinology, Infectious Diseases and Metabolism, University Hospital Marburg, 35043 Marburg, Germany.
Background: Most spheroid models use size measurements as a primary readout parameter; some models extend analysis to T cell infiltration or perform caspase activation assays. However, to our knowledge, T cell motility analysis is not regularly included as an endpoint in imaging studies on cancer spheroids.
Methods: Here, we intend to demonstrate that motility analysis of macrophages and T cells is a valuable functional endpoint for studies on molecular interventions in the tumor microenvironment.
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