학술논문
Tumour infiltrating B cells discriminate checkpoint blockade-induced responses.
Document Type
Academic Journal
Author
Valpione S; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom. Electronic address: sara.valpione@cruk.manchester.ac.uk.; Campana LG; Department of Surgery, Manchester University NHS Foundation Trust, Manchester, United Kingdom.; Weightman J; Molecular Biology Core Facility, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Salih Z; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.; Galvani E; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Mundra PA; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; De Rosa F; Immunotherapy and Rare Tumours Unit, Istituto Scientifico Romagnolo per Lo Studio e La Cura Dei Tumori (IRST) 'Dino Amadori' IRCCS, Meldola (FC) 47014, Italy.; Gupta A; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.; Serra-Bellver P; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.; Lorigan P; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.; Germetaki T; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.; Dynowski M; Scientific Computing, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Kitcatt S; Scientific Computing, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Sahoo S; Computational Biology Support Team, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Lee D; Computational Biology Support Team, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Dhomen N; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom.; Lord G; School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, United Kingdom.; Marais R; Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, United Kingdom. Electronic address: richard.marais@cruk.manchester.ac.uk.
Source
Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Immune cell-driven anti-cancer activity is paramount for effective responses to checkpoint inhibitors (ICB). However, the contribution of the different immune cell subsets in the circulation and within the tumour is poorly understood.
Materials and Methods: To elucidate the role of the different cell subsets in anti-tumour responses elicited by ICB, we performed single-cell analysis of the transcriptome and surface proteome of paired pre- and early on-treatment metastatic melanoma tumour biopsies and matched peripheral blood mononuclear cell samples. We next compared the survival of metastatic melanoma patients treated with ICB according to the abundance of pre-treatment tumour-infiltrating B cell clonotypes.
Results: We identified cell clusters associated with disease control or progression, defined differential expression of biological pathways likely involved in the immune awakening against the tumour and examined how cell-cell communication patterns between the tumour cell subsets change during treatment. Furthermore, we discovered that B cells (immunoglobulin expression and abundance of B cell clonotypes) discriminate the clinical response after ICB and propose that B cells likely contribute to anti-tumour immunity by antigen presentation through major histocompatibility complex molecules. Finally, we demonstrated that the abundance of tumour-infiltrating B cell clonotypes at baseline identifies two distinct risk groups, a finding that we confirmed in an independent cohort.
Conclusions: Our exploratory translational study provides new insights on the mechanistic role of B cells in anti-melanoma immunity during treatment with ICB. Additionally, we support pre-treatment B cell tumour infiltration as a promising prognostic biomarker to be further validated as a tool for clinical risk stratification.
Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Materials and Methods: To elucidate the role of the different cell subsets in anti-tumour responses elicited by ICB, we performed single-cell analysis of the transcriptome and surface proteome of paired pre- and early on-treatment metastatic melanoma tumour biopsies and matched peripheral blood mononuclear cell samples. We next compared the survival of metastatic melanoma patients treated with ICB according to the abundance of pre-treatment tumour-infiltrating B cell clonotypes.
Results: We identified cell clusters associated with disease control or progression, defined differential expression of biological pathways likely involved in the immune awakening against the tumour and examined how cell-cell communication patterns between the tumour cell subsets change during treatment. Furthermore, we discovered that B cells (immunoglobulin expression and abundance of B cell clonotypes) discriminate the clinical response after ICB and propose that B cells likely contribute to anti-tumour immunity by antigen presentation through major histocompatibility complex molecules. Finally, we demonstrated that the abundance of tumour-infiltrating B cell clonotypes at baseline identifies two distinct risk groups, a finding that we confirmed in an independent cohort.
Conclusions: Our exploratory translational study provides new insights on the mechanistic role of B cells in anti-melanoma immunity during treatment with ICB. Additionally, we support pre-treatment B cell tumour infiltration as a promising prognostic biomarker to be further validated as a tool for clinical risk stratification.
Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)