Poor clinical response rates have been observed in the majority of the T cell-based immunotherapy clinical trials conducted to date. One reason might be the presence of abnormalities in HLA class I antigen presentation in malignant lesions. An increased frequency of HLA class I abnormalities has been observed in malignant lesions from patients treated with T cell-based immunotherapy and in lesions which have recurred in patients who had experienced clinical responses following T cell-based immunotherapy. These observations are compatible with the possibility that the outgrowth of a patient's tumor reflects immune selection of tumor cells which have acquired escape mechanisms from immune recognition.
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http://dx.doi.org/10.1016/s0264-410x(02)00386-9 | DOI Listing |
JID Innov
March 2025
Department of Dermatology, University Hospital of Zurich, University of Zurich, Schlieren, Switzerland.
In cutaneous melanoma, epigenetic dysregulation is implicated in drug resistance and tumor immune escape. However, the epigenetic mechanisms that influence immune escape remain poorly understood. To elucidate how epigenetic dysregulation alters the expression of surface proteins that may be involved in drug targeting and immune escape, we performed a 3-dimensional surfaceome screen in primary melanoma cultures and identified the DNA-methyltransferase inhibitor decitabine as significantly upregulating the costimulatory molecule ICAM-1.
View Article and Find Full Text PDFImmunohorizons
January 2025
Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, United States.
Antibody (Ab) crosslinking of HLA class II (HLA II) molecules on the surface of endothelial cells (ECs) triggers proliferative and prosurvival intracellular signaling, which are implicated in promoting chronic Ab-mediated rejection (cAMR). Despite the importance of cAMR in transplant medicine, the mechanisms involved remain incompletely understood. Here, we examined the regulation of yes-associated protein (YAP) nuclear cytoplasmic localization and phosphorylation in human ECs challenged with Abs that bind HLA II, which are strongly associated with cAMR.
View Article and Find Full Text PDFInt J Immunogenet
January 2025
Department of Clinical Haematology and Medical Oncology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
High degree of variability in human leukocyte antigens (HLAs) system restricts availability of histocompatible HLA-matched-related donors, thus increasing reliance on worldwide bone marrow registries network. Nevertheless, due to limited coverage/accessibility/affordability of some ethnicities in these registries, haploidentical haematopoietic stem cell transplantation (HSCT) emerged as an alternative option, though with allorecognition-mediated graft versus host disease (GvHD) (>40% cases). A dimorphism [-21 methionine (M) or threonine (T)] in HLA-B leader peptide (exon 1) which differentially influences its HLA-E binding, plausibly regulates natural killer cell functionality, affecting GvHD vulnerability and clinically in practice for donor selection.
View Article and Find Full Text PDFHLA
January 2025
Servicio de Inmunología, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Description of two novel HLA class II alleles, DPB1*1626:01Q and DRB1*11:337 alleles.
View Article and Find Full Text PDFMol Immunol
January 2025
Department of Medical Laboratory Center, General Hospital of Central Theater Command, Wuhan, Hubei 430015, PR China. Electronic address:
Purpose: SARS-CoV-2-specific CD8 cytotoxic T lymphocytes (CTLs) are crucial in viral clearance, disease progression, and reinfection control. However, numerous SARS-CoV-2 immunodominant CTL epitopes theoretically are still unidentified due to the genetic polymorphism of human leukocyte antigen class I (HLA-I) molecules.
Methods: The CTL epitopes of SARS-CoV-2 were predicted by the epitope affinity and immunogenicity prediction platforms: the NetMHCpan and the PromPPD.
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