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 Vöhringer, Berit J. Brinkmann, Felix Czernilofsky, Mareike Knoll, Laura Llaó Cid, Anna Mathioudaki, Bianca Faßbender, Maxime Herbon, Tobias Lautwein, Peter‐Martin Bruch, Nora Liebers, Christian M. Schürch, Verena Passerini, Marc Seifert, Alexander Brobeil, Gunhild Mechtersheimer, Carsten Müller‐Tidow, Oliver Weigert, Martina Seiffert, Garry P. Nolan, Wolfgang Huber, Sascha Dietrich · 发表于：Nature Cell Biology · 年份：2024 · DOI：10.1038/s41556-024-01358-2 · 被引用次数：69 · 研究领域：CAR-T cell therapy research、T-cell and B-cell Immunology、Immune Cell Function and Interaction

Abstract The redirection of T cells has emerged as an attractive therapeutic principle in B cell non-Hodgkin lymphoma (B-NHL). However, a detailed characterization of lymphoma-infiltrating T cells across B-NHL entities is missing. Here we present an in-depth T cell reference map of nodal B-NHL, based on cellular indexing of transcriptomes and epitopes, T cell receptor sequencing, flow cytometry and multiplexed immunofluorescence applied to 101 lymph nodes from patients with diffuse large B cell, mantle cell, follicular or marginal zone lymphoma, and from healthy controls. This multimodal resource revealed quantitative and spatial aberrations of the T cell microenvironment across and within B-NHL entities. Quantitative differences in PD1 + TCF7 − cytotoxic T cells, T follicular helper cells or IKZF3 + regulatory T cells were linked to their clonal expansion. The abundance of PD1 + TCF7 − cytotoxic T cells was associated with poor survival. Our study portrays lymphoma-infiltrating T cells with unprecedented comprehensiveness and provides a unique resource for the investigation of lymphoma biology and prognosis.