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

Marc A Baertsch, Garry P Nolan, Martina Seiffert, Oliver Weigert, Alexander Brobeil, Marc Seifert, Verena Passerini, Tobias Lautwein, Maxime Herbon, Bianca Faßbender, Anna Mathioudaki, Laura Llaó-Cid, Harald Vöhringer, Donnacha Fitzgerald, Sascha Dietrich, Wolfgang Huber, Carsten Müller-Tidow, Mareike Knoll, Peter-Martin Bruch, Tobias Roider, Felix Czernilofsky, Berit J Brinkmann, Nora Liebers, Christian M Schürch, Gunhild Mechtersheimer

Journal: Nature cell biology 2024;26(3):478-489

PMID: 38379051

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.

© 2024. The Author(s).

Address: Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.; Molecular Medicine Partnership Unit, Heidelberg, Germany.; European Molecular Biology Laboratory, Heidelberg, Germany.; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.; Molecular Medicine Partnership Unit, Heidelberg, Germany.; European Molecular Biology Laboratory, Heidelberg, Germany.; Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center, Heidelberg, Germany.; European Molecular Biology Laboratory, Heidelberg, Germany.; Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.; Molecular Pathology of Lymphoid Neoplasms, Fundació de Recerca Clinic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS), Barcelona, Spain.; Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany.; Genomics and Transcriptomics Laboratory, University of Düsseldorf, Düsseldorf, Germany.; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.; Molecular Medicine Partnership Unit, Heidelberg, Germany.; European Molecular Biology Laboratory, Heidelberg, Germany.; Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany.; European Molecular Biology Laboratory, Heidelberg, Germany.; Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany.; National Center for Tumor Diseases, Heidelberg, Germany.; German Cancer Research Center, Heidelberg, Germany.; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.; Department of Medicine III, Laboratory for Experimental Leukemia and Lymphoma Research, Ludwig-Maximilians-University Hospital, Munich, Germany.; Department of Pathology, University of Heidelberg, Heidelberg, Germany.; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany.; Molecular Medicine Partnership Unit, Heidelberg, Germany.; German Cancer Research Center, Heidelberg, Germany.; Department of Medicine III, Laboratory for Experimental Leukemia and Lymphoma Research, Ludwig-Maximilians-University Hospital, Munich, Germany.; German Cancer Consortium, Munich, Germany.; Division of Molecular Genetics, German Cancer Research Center, Heidelberg, Germany.; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.; Molecular Medicine Partnership Unit, Heidelberg, Germany. [email protected].; European Molecular Biology Laboratory, Heidelberg, Germany. [email protected].; Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Heidelberg, Germany. [email protected].; Molecular Medicine Partnership Unit, Heidelberg, Germany. [email protected].; European Molecular Biology Laboratory, Heidelberg, Germany. [email protected].; Department of Hematology and Oncology, University Hospital Düsseldorf, Düsseldorf, Germany. [email protected].; Center for Integrated Oncology Aachen-Bonn-Cologne-Düsseldorf (CIO ABCD), Aachen Bonn Cologne Düsseldorf, Germany. [email protected].
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