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Decreased number of granzyme B+ activated CD8+ cytotoxic T lymphocytes in the inflammatory background of HIV-associated Hodgkin’s lymphoma

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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.

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Acknowledgements

The authors are grateful to all the participants of the Spanish Hodgkin’s lymphoma Study Group for their cooperation and to the National Center of Oncology Investigation (CNIO) of Madrid for the TMAs. We are also indebted to Dra. Silvia de Sanjosé (Servei d’Epidemiologia i Registre del Càncer of ICO) for her scientific revision of the manuscript and with Fernando Romeu (EOI Tortosa) for improving the text (language) of our paper.

This study was supported by grants from the Ministerio de Sanidad y Consumo, Spain (grant PI021367, grant G03/179, grant PI041467, and grant PI041440).

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Authors and Affiliations

  1. Department of Pathology, Hospital de Tortosa Verge de la Cinta, C/Esplanetes No. 44–56, 43500, Tortosa, Spain

    Ramón Bosch Príncep, Marylène Lejeune, Maria Teresa Salvadó Usach, Joaquín Jaén Martínez, Lluis E. Pons Ferré & Tomás Álvaro Naranjo

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  1. Ramón Bosch Príncep
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  2. Marylène Lejeune
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  3. Maria Teresa Salvadó Usach
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Correspondence to Ramón Bosch Príncep.

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Bosch Príncep, R., Lejeune, M., Salvadó Usach, M.T. et al. Decreased number of granzyme B+ activated CD8+ cytotoxic T lymphocytes in the inflammatory background of HIV-associated Hodgkin’s lymphoma. Ann Hematol 84, 661–666 (2005). https://doi.org/10.1007/s00277-005-1051-3

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