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Immune phenotypes and checkpoint molecule expression of clonally expanded lymph node-infiltrating T cells in classical Hodgkin lymphoma

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Item Type:Article
Title:Immune phenotypes and checkpoint molecule expression of clonally expanded lymph node-infiltrating T cells in classical Hodgkin lymphoma
Creators Name:Ballhausen, A. and Ben Hamza, A. and Welters, C. and Dietze, K. and Bullinger, L. and Rahn, H.P. and Hartmann, S. and Hansmann, M.L. and Hansmann, L.
Abstract:Lymph node-infiltrating T cells have been of particular interest in classical Hodgkin lymphoma (cHL). High rates of complete therapeutic responses to antibody-mediated immune checkpoint blockade, even in relapsed/refractory patients, suggest the existence of a T cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed immune microenvironment. We asked whether clonally expanded T cells (1) were detectable in cHL lymph nodes, (2) showed characteristic immune phenotypes, and (3) were inhibited by immune checkpoint molecule expression. We applied high-dimensional FACS index sorting and single cell T cell receptor αβ sequencing to lymph node-infiltrating T cells from 10 treatment-naïve patients. T cells were predominantly CD4(+) and showed memory differentiation. Expression of classical immune checkpoint molecules (CTLA-4, PD-1, TIM-3) was generally low (< 12.0% of T cells) and not different between CD4(+) and CD8(+) T cells. Degrees of clonal T cell expansion varied between patients (range: 1-18 expanded clones per patient) and was almost exclusively restricted to CD8(+) T cells. Clonally expanded T cells showed non-naïve phenotypes and low checkpoint molecule expression similar to non-expanded T cells. Our data suggest that the therapeutic effects of immune checkpoint blockade require mechanisms in addition to dis-inhibition of pre-existing lymphoma-directed T cell responses. Future studies on immune checkpoint blockade-associated effects will identify molecular T cell targets, address dynamic aspects of cell compositions over time, and extend their focus beyond lymph node-infiltrating T cells.
Keywords:Hodgkin Lymphoma, Lymph Node-Infiltrating T Cells, Immune Checkpoint Blockade, Lymphoma, Immunology, Single Cell Technologies, T Cell Receptor Sequencing
Source:Cancer Immunology Immunotherapy
ISSN:0340-7004
Publisher:Springer
Date:10 August 2022
Official Publication:https://doi.org/10.1007/s00262-022-03264-8
PubMed:View item in PubMed

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