| Autor: |
Tobias Roider, Marc A. Baertsch, Donnacha Fitzgerald, Harald Voehringer, Berit J. Brinkmann, Felix Czernilofsky, Mareike Knoll, Laura Llaó-Cid, Peter-Martin Bruch, Nora Liebers, Christian M. Schürch, Verena Passerini, Alexander Brobeil, Gunhild Mechtersheimer, Carsten Müller-Tidow, Oliver Weigert, Martina Seiffert, Garry P. Nolan, Wolfgang Huber, Sascha Dietrich |
| Rok vydání: |
2022 |
| Popis: |
SummaryT-cell-engaging immunotherapies have improved the treatment of nodal B-cell lymphoma, but responses vary highly. Future improvements of such therapies require better understanding of the variety of lymphoma-infiltrating T-cells. We employed single-cell RNA and T-cell receptor sequencing alongside quantification of surface proteins, flow cytometry and multiplexed immunofluorescence on 101 lymph nodes from healthy controls, and patients with diffuse large B-cell, mantle cell, follicular, or marginal zone lymphoma. This multimodal resource revealed entity-specific quantitative and spatial aberrations of the T-cell microenvironment. Clonal PD1+TCF7-but not PD1+TCF7+cytotoxic T-cells converged into terminally exhausted T-cells, the proportions of which were variable across entities and linked to inferior prognosis. In follicular and marginal zone lymphoma, we observed expansion of follicular helper and IKZF3+regulatory T-cells, which were clonally related and inversely associated with tumor grading. Overall, we portray lymphoma-infiltrating T-cells with unprecedented comprehensiveness and decipher both beneficial and adverse dimensions of T-cell response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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