title: High numbers of tumour-infiltrating activated cytotoxic T lymphocytes, and frequent loss of HLA class I and II expression, are features of aggressive B cell lymphomas of the brain and testis.
abstract: 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.
authors.affiliation: Department of Pathology, Leiden University Medical Centre, Leiden, The Netherlands. s.riemersma@aborpath.nl
authors.forename: Sietske A
authors.initials: SA
authors.lastname: Riemersma
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
authors.forename: Marcel J
authors.initials: MJ
authors.lastname: Vonk
authors.forename: Enno J
authors.initials: EJ
authors.lastname: Dreef
authors.forename: Frans A
authors.initials: FA
authors.lastname: Prins
authors.forename: Patty M
authors.initials: PM
authors.lastname: Jansen
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: Paul
authors.initials: P
authors.lastname: Blok
authors.forename: Robbie E
authors.initials: RE
authors.lastname: Kibbelaar
authors.forename: Jettie J F
authors.initials: JJ
authors.lastname: Muris
authors.forename: Ed M D
authors.initials: EM
authors.lastname: Schuuring
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kluin
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000276:immunology; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis / Q000235:genetics; D016827:CD8 Antigens / Q000032:analysis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D018655:Lymphocyte Count / Q000379:methods; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000276:immunology; D008297:Male; D010641:Phenotype; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013736:Testicular Neoplasms / Q000235:genetics* / Q000276:immunology
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II