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