CXCR5 and ICOS expression identifies a CD8 T-cell subset with T features in Hodgkin lymphomas

Abstract : A better characterization of T-cell subsets in the microenvironment of classical Hodgkin lymphoma (cHL) would help to develop immunotherapies. Using multicolor flow cytometry, we identified in 6 of 43 cHL tissue samples a previously unrecognized subset of CD8 T cells coexpressing CXCR5 and inducible T-cell costimulator (ICOS) molecules (CD8). These cells shared phenotypic features with follicular helper T (T) cells including low CCR7 expression together with high expression of B-cell lymphoma-6, programmed cell death 1, B and T lymphocyte attenuator, CD200, and OX40. They had deficient cytotoxicity, low interferon-γ secretion, and common functional properties with intratumoral CD4 T cells, such as production of interleukin-4 (IL-4), IL-21, CXCL13, and capacity to sustain B cells. Gene profiling analysis showed a significant similarity between the signatures of CD8 T cells and CD4 T cells. Benign lymphadenitis tissues (n = 8) were devoid of CD8 cells. Among the 35 B-cell lymphoma tissues analyzed, including follicular lymphomas (n = 13), diffuse large cell lymphomas (n = 12), marginal zone lymphomas (MZLs; n = 3), mantle cell lymphomas (n = 3), and chronic lymphocytic leukemias (n = 4), only 1 MZL sample contained CD8 cells. Lymphoma tumors with CD8 cells shared common histopathological features including residual germinal centers, and contained high amounts of activated CD8 cells. These data demonstrate a CD8 T-cell differentiation pathway leading to the acquisition of some T similarities. They suggest a particular immunoediting process with global CD8 activation acting mainly, but not exclusively, in HL tumors.
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Submitted on : Tuesday, August 28, 2018 - 1:53:48 PM
Last modification on : Thursday, December 20, 2018 - 11:18:38 AM

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Kieu-Suong Le, Patricia Amé-Thomas, Karin Tarte, Françoise Gondois-Rey, Samuel Granjeaud, et al.. CXCR5 and ICOS expression identifies a CD8 T-cell subset with T features in Hodgkin lymphomas. Blood Advances, The American Society of Hematology, 2018, 2 (15), pp.1889-1900. ⟨10.1182/bloodadvances.2018017244⟩. ⟨hal-01863383⟩

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