title: Decreased number of granzyme B+ activated CD8+ cytotoxic T lymphocytes in the inflammatory background of HIV-associated Hodgkin's lymphoma.
abstract: This study aimed to assess the differences in the cellular composition of the inflammatory reactive background around tumoral cells of classical Hodgkin's lymphomas (cHL) inside and outside the HIV settings. This retrospective study evaluates the infiltrating T lymphocytes (CD4 and CD8), natural killer cells (CD57+ cells), and more especially cytotoxic cells [granzyme B (GrB) and TIA-1+ cells] in the background of 99 EBV+ cHL. Sections from paraffin-embedded tumor samples from nine HIV-infected cHL patients were immunostained, using standard immunohistochemical protocols and were compared to a control group of 90 HIV-noninfected cHL patients. Our clinical and histological data indicate that HIV-infected cHL patients present a higher frequency of mixed cellularity (MC) histological subtypes, more advanced disease stages, a poor response to treatment, and a poor overall survival compared to control patients. In controls, CD4/CD8 and GrB/TIA-1 ratios were determined as 2:1 and 1:2, respectively. The inflammatory infiltrate of HIV-infected patients had a significant reduction of CD4+ T lymphocytes (CD4/CD8 ratio 1:23), a decrease in infiltrating GrB+ cells (activated cytotoxic cells) and an increase in infiltrating TIA+ T cells (mainly nonactivated cytotoxic cells) in these patients (GrB/TIA-1 ratio 1:12). In conclusion, this study highlights an important intratumoral loss of CD4+ T cells (striking inversion in the CD4/CD8 ratio) and a decrease in intratumoral activated cytotoxic T lymphocytes in HIV-associated cHL patients. Further studies are required to confirm these results and to determine the role of these findings on the antitumoral immune response observed in HIV-associated cHL.
authors.affiliation: Department of Pathology, Hospital de Tortosa Verge de la Cinta, C/Esplanetes No. 44-56, 43500 Tortosa, Spain. rbosch.htvc.ics@gencat.net
authors.forename: Ramón
authors.initials: R
authors.lastname: Bosch Príncep
authors.forename: Marylène
authors.initials: M
authors.lastname: Lejeune
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Salvadó Usach
authors.forename: Joaquín
authors.initials: J
authors.lastname: Jaén Martínez
authors.forename: Lluis E
authors.initials: LE
authors.lastname: Pons Ferré
authors.forename: Tomás
authors.initials: T
authors.lastname: Alvaro Naranjo
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016516:CD4-CD8 Ratio / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D053804:Granzymes; D006678:HIV; D015658:HIV Infections / Q000150:complications / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D006689:Hodgkin Disease / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000821:virology; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism; D012189:Retrospective Studies; D012697:Serine Endopeptidases / Q000378:metabolism*; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D014408:Biomarkers, Tumor; D039102:Poly(A)-Binding Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases