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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., Ben Hamza, A., Welters, C., Dietze, K., Bullinger, L., Rahn, H.P., Hartmann, S., 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 |
| Volume: | 72 |
| Number: | 2 |
| Page Range: | 515-521 |
| Date: | February 2023 |
| Official Publication: | https://doi.org/10.1007/s00262-022-03264-8 |
| PubMed: | View item in PubMed |
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