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

Nat Cell Biol. 2024 Mar;26(3):478-489. doi: 10.1038/s41556-024-01358-2.

Tobias Roider ^# ¹ ² ³, Marc A Baertsch ^# ¹ ⁴, Donnacha Fitzgerald ¹ ² ³, Harald Vöhringer ¹ ² ³, Berit J Brinkmann ¹ ² ³ ⁵, Felix Czernilofsky ¹ ² ³, Mareike Knoll ³, Laura Llaó-Cid ⁶ ⁷, Anna Mathioudaki ³, Bianca Faßbender ⁸, Maxime Herbon ⁸, Tobias Lautwein ⁹, Peter-Martin Bruch ¹ ² ³ ⁸, Nora Liebers ³ ⁸ ¹⁰ ¹¹, Christian M Schürch ⁴ ¹², Verena Passerini ¹³, Marc Seifert ⁸, Alexander Brobeil ¹⁴, Gunhild Mechtersheimer ¹⁴, Carsten Müller-Tidow ¹ ², Oliver Weigert ¹¹ ¹³ ¹⁵, Martina Seiffert ⁶, Garry P Nolan ¹⁶, Wolfgang Huber ¹⁷ ¹⁸, Sascha Dietrich ¹⁹ ²⁰ ²¹ ²² ²³

Affiliations

1 Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.
2 Molecular Medicine Partnership Unit, Heidelberg, Germany.
3 European Molecular Biology Laboratory, Heidelberg, Germany.
4 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
5 Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany.
6 Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.
7 Molecular Pathology of Lymphoid Neoplasms, Fundació de Recerca Clinic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain.
8 Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany.
9 Genomics and Transcriptomics Laboratory, University of Düsseldorf, Düsseldorf, Germany.
10 National Center for Tumor Diseases, Heidelberg, Germany.
11 German Cancer Research Center, Heidelberg, Germany.
12 Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.
13 Department of Medicine III, Laboratory for Experimental Leukemia and Lymphoma Research, Ludwig-Maximilians-University Hospital, Munich, Germany.
14 Department of Pathology, University of Heidelberg, Heidelberg, Germany.
15 German Cancer Consortium, Munich, Germany.
16 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
17 Molecular Medicine Partnership Unit, Heidelberg, Germany. wolfgang.huber@embl.de.
18 European Molecular Biology Laboratory, Heidelberg, Germany. wolfgang.huber@embl.de.
19 Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany. sascha.dietrich@embl.de.
20 Molecular Medicine Partnership Unit, Heidelberg, Germany. sascha.dietrich@embl.de.
21 European Molecular Biology Laboratory, Heidelberg, Germany. sascha.dietrich@embl.de.
22 Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany. sascha.dietrich@embl.de.
23 Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Aachen Bonn Cologne Düsseldorf, Germany. sascha.dietrich@embl.de.
# Contributed equally.

PMID: 38379051 DOI: 10.1038/s41556-024-01358-2

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.

Name
Email *

	Sorry, but the email address you supplied was invalid.