title: Prognostic significance of activated cytotoxic T-lymphocytes in primary nodal diffuse large B-cell lymphomas.
abstract: Clinical outcome in diffuse large B-cell lymphoma (DLBCL) remains unpredictable, despite the identification of clinical prognostic parameters. Here, we investigated in pretreatment biopsies of 70 patients with DLBCL whether numbers of activated cytotoxic T-lymphocytes (CTLs), as determined by the percentage of CD3-positive lymphocytes with granzyme B (GrB) expression, have similar prognostic value as found earlier in Hodgkin's lymphoma and anaplastic large-cell lymphoma and whether loss of major histocompatibility complex (MHC)-I molecules or expression of the GrB antagonist protease inhibitor 9 (PI9) may explain immune escape from CTL-mediated cell death. Independent of the International Prognostic Index (IPI), the presence of >/=15% activated CTLs was strongly associated with failure to reach complete remission, with a poor progression-free and overall survival time. Downregulation of MHC-I light- and/or heavy-chain expression was found in 41% of interpretable cases and in 19 of 56 interpretable cases PI9 expression was detected. We conclude that a high percentage of activated CTLs is a strong, IPI independent, indicator for an unfavorable clinical outcome in patients with primary nodal DLBCL. Although in part of DLBCL expression of PI9 and loss of MHC-I expression was found, providing a possible immune-escape mechanism in these cases, no correlation with clinical outcome was found.
authors.affiliation: Department of Clinical Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
authors.forename: J J F
authors.initials: JJ
authors.lastname: Muris
authors.forename: C J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: S A G M
authors.initials: SA
authors.lastname: Cillessen
authors.forename: W
authors.initials: W
authors.lastname: Vos
authors.forename: J A
authors.initials: JA
authors.lastname: Kummer
authors.forename: B A
authors.initials: BA
authors.lastname: Bladergroen
authors.forename: M J J T
authors.initials: MJ
authors.lastname: Bogman
authors.forename: M A
authors.initials: MA
authors.lastname: MacKenzie
authors.forename: N M
authors.initials: NM
authors.lastname: Jiwa
authors.forename: L H
authors.initials: LH
authors.lastname: Siegenbeek van Heukelom
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: J J
authors.initials: JJ
authors.lastname: Oudejans
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D005805:Genes, MHC Class I / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D008297:Male; D008868:Microtubule Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000378:metabolism; D011379:Prognosis; D050777:Stathmin; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D008868:Microtubule Proteins; D010750:Phosphoproteins; C493995:STMN1 protein, human; D050777:Stathmin