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Loss of both HLA class I and class II expression in B cell lymphomas is a mechanism of escape from a cytotoxic T lymphocyte (CTL) immune response and will therefore give a strong selective survival advantage in tumours expressing strong immunogenic antigens. We investigated loss of HLA expression using specific antibodies on tissue sections from 254 B cell lymphomas originating from nodal and different extranodal sites in relation to numbers of tumour-infiltrating T cells. Complete loss of HLA class I and II was observed in a minority of the nodal, stomach, and skin lymphomas but in the majority of the lymphomas originating from the testis and the CNS. Interestingly, relatively high percentages of activated CTLs were detected in both primary testicular and CNS lymphomas compared to lymphomas at other sites, with highest percentages in the testis (p < 0.0001). We conclude that loss of both HLA class I and II expression occurs very frequently in lymphomas originating from the testis and the CNS as compared to nodal and some other extranodal sites. The presence of high percentages of activated CTLs in the testicular and CNS lymphomas suggests that loss of HLA expression provides a strong growth advantage for lymphoma cells in these immune-privileged sites.
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http://dx.doi.org/10.1002/path.1783 | DOI Listing |
Am J Hematol
September 2025
Université D'angers, Université de Nantes, Inserm, CNRS, CRCI2NA, SFR ICAT, Angers, France.
Loss of function mutations in the gene encoding WASP (Wiskott-Aldrich syndrome protein) result in Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia-XLT (WAS/XLT). The clinical severity of the disease can be assessed using the WAS clinical severity score. Typically, patients with a score of 3 or less at 2 years of age are considered to have mild WAS/XLT disease.
View Article and Find Full Text PDFNAR Cancer
September 2025
Division of Oncogenomics, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
The presentation of peptides on HLA molecules is essential to CD8 T cell responses. Here, we show that loss of uL14 significantly downregulates the expression of antigen processing and presentation (APP) components in melanoma cell lines. Peptides generated following knockdown show different characteristics, with altered peptide charge, and differences in anchor residue positions.
View Article and Find Full Text PDFAm J Hematol
September 2025
Department of Hematology, Tohoku University Hospital, Sendai, Japan.
HLA class I allele loss in acquired aplastic anemia (AA) represents an immune escape from the T cell-mediated pathogenesis. We investigated the impact of loss-prone HLA alleles on the hematopoietic cell transplantation (HCT) outcomes using registry data of 875 Japanese patients with acquired AA. HLA associations were evident exclusively among 399 patients who received HCT within 1 year of the diagnosis, consistent with the predominance of HLA loss in this group.
View Article and Find Full Text PDFAm J Reprod Immunol
September 2025
Department of Molecular Biology and Genetics, Tokat Gaziosmanpasa University, Tokat, Türkiye.
Problem: Interferon-ε (IFNε), which is highly abundant in the epithelium of the female reproductive tract (FRT), is a recently identified tumor suppressor for ovarian cancer. IFNε induces the expression of certain HLA class I family members in HGSOC (high-grade serous ovarian cancer), and its expression is lost during ovarian tumorigenesis. However, tumor stage-dependent expression of HLA class I family members in ovarian cancer has not been previously studied.
View Article and Find Full Text PDFTranspl Int
August 2025
Department of Internal Medicine, Division of Nephrology and Transplantation, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, Netherlands.
HLA molecular matching in solid organ transplantation in the form of eplets, solvent-accessible amino acids or PIRCHE-II has been proposed as a more granular method than HLA matching on the antigen level. While many studies have shown the association between molecular mismatches and donor-specific antibody formation, rejection and graft loss, evidence for prospective molecular matching in allocation is currently lacking, and the actual practical implementation and feasibility of molecular matching remains unclear. In this review the various potential applications of molecular matching in transplantation are discussed, including 1) organ allocation in deceased donor programs, 2) living donor selection, 3) increasing the transplantability of highly sensitized patients and 4) risk stratification to facilitate personalized immunosuppressive management, along with the challenges and gaps in current knowledge regarding these approaches.
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