Multimodal and spatially resolved profiling identifies distinct patterns of T-cell infiltration in nodal B-cell lymphoma entities

作者：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 K. Huber, Sascha Dietrich · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2022 · DOI：10.1101/2022.11.04.514366 · 被引用次数：11 · 研究领域：CAR-T cell therapy research、Single-cell and spatial transcriptomics、Immune Cell Function and Interaction

Summary T-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.