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Prof. Dr. Sophia Karagiannis

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Guest Editor

Translational Cancer Immunology and Immunotherapy, St. John’s Institute of Dermatology, School of Basic & Medical Biosciences, King's College London, London SE1 9RT, UK
Interests: B cell responses in cancer; antibody engineering and glycoengineering; IgE class of antibodies in cancer; antibody Fc-mediated functions in cancer; cancer immunology; cancer immunotherapy; antibody-drug conjugates; melanoma; ovarian cancer; breast cancer; allergo-oncology; ADCC; ADCP; macrophages; monocytes; NK cells
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Dr. Joseph G Crompton

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Guest Editor

Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA
Interests: tertiary lymphoid structures
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A better understanding of the role of B cells in orchestrating an antitumor response has the potential to broaden the efficacy of immunotherapy for patients with advanced cancer. While the role of T cells in cancer immunology has been studied extensively, a fulsome understanding of B cell populations and effector mechanisms mediating humoral immunity against cancer has not been carefully elucidated. Although many causal mechanisms of humoral antitumor immunity have not yet been described, strong positive correlations between B cells and cancer-specific survival and response to therapy have recently been reported. Many studies have demonstrated that the presence of intratumoral B cells is strongly associated with survival in several histologies, including sarcoma, melanoma, lung, and colorectal cancer. This Special issue will summarize several topics related to humoral antitumor immunity, including the dual role of B cells in promoting and inhibiting cancer, the antitumor functions of B cells such as antibody-dependent cell cytotoxicity, mechanisms of tumor-antigen presentation by B cells, the importance of cancer-associated tertiary lymphoid structures, and the impact of immunoglobin repertoire and isotype on cancer immunosurveillance. Finally, we will assemble an up-to-date review on recent advances in developing B cell-based immunotherapies and vaccines for the treatment of advanced cancers.

Prof. Dr. Sophia Karagiannis
Dr. Joseph G Crompton
Guest Editors

Manuscript Submission Information

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Keywords

cancer and B cells
humoral antitumor immunity
cancer-associated tertiary lymphoid structures
immune surveillance
immunotherapy

Published Papers (2 papers)

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Research

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21 pages, 23622 KiB

Open AccessArticle

Ibrutinib Inhibits BTK Signaling in Tumor-Infiltrated B Cells and Amplifies Antitumor Immunity by PD-1 Checkpoint Blockade for Metastatic Prostate Cancer

by Gengguo Deng, Jiannan He, Qunxiong Huang, Tengcheng Li, Zhansen Huang, Shuntian Gao, Jinbin Xu, Tiantian Wang and Jinming Di

Cancers 2023, 15(8), 2356; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082356 - 18 Apr 2023

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Abstract

Metastatic prostate cancer (PCa) remains incurable and causes considerably diminished overall survival. Despite significant progress in pharmacotherapy, the disease prognosis remains unchanged. Immune checkpoint inhibitors (ICIs) have demonstrated effectiveness in treating various advanced malignancies, but their efficacy in metastatic PCa is relatively limited. Previous studies have confirmed the immunosuppressive role of tumor-infiltrating B cells (TIL-Bs) in the PCa microenvironment, which accounts for their poor immunogenic potency. In this study, we demonstrated that an oral kinase agent, ibrutinib, strongly potentiated anti-PD-1 checkpoint blockade efficacy and successfully controlled tumor growth in a murine orthotopic PCa model constructed using a metastatic and hormone-independent cell line (RM-1). We identified close relationships between TIL-Bs, Bruton’s tyrosine kinase (BTK), and immunosuppressive molecules by bioinformatics and histological analysis. An in vitro study showed that a low dose of ibrutinib significantly inhibited B cell proliferation and activation as well as IL-10 production through the BTK pathway. Moreover, ibrutinib-treated B cells promoted CD8⁺ T cell proliferation and inhibitory receptor (IR) expression. However, the same dose of ibrutinib was insufficient to induce apoptosis in cancer cells. An in vivo study showed that ibrutinib monotherapy failed to achieve tumor regression in murine models but decreased B cell infiltration and inhibited activation and IL-10 production. More importantly, CD8⁺ T cell infiltration increased with high IR expression. Ibrutinib synergized with anti-PD-1 checkpoint blockade enormously improved antitumor immunity, thereby reducing tumor volume in the same scenario. These data set the scene for the clinical development of ibrutinib as an immunogenic trigger to potentiate anti-PD-1 checkpoint blockade for metastatic PCa immunotherapy. Full article

(This article belongs to the Special Issue B Cells and Antibodies in Immune Surveillance and Therapy for Cancer)

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Review

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19 pages, 2346 KiB

Open AccessReview

B Cells in Breast Cancer Pathology

by Mengyuan Li, Angela Quintana, Elena Alberts, Miu Shing Hung, Victoire Boulat, Mercè Martí Ripoll and Anita Grigoriadis

Cancers 2023, 15(5), 1517; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15051517 - 28 Feb 2023

Cited by 3 | Viewed by 3737

Abstract

B cells have recently become a focus in breast cancer pathology due to their influence on tumour regression, prognosis, and response to treatment, besides their contribution to antigen presentation, immunoglobulin production, and regulation of adaptive responses. As our understanding of diverse B cell subsets in eliciting both pro- and anti-inflammatory responses in breast cancer patients increases, it has become pertinent to address the molecular and clinical relevance of these immune cell populations within the tumour microenvironment (TME). At the primary tumour site, B cells are either found spatially dispersed or aggregated in so-called tertiary lymphoid structures (TLS). In axillary lymph nodes (LNs), B cell populations, amongst a plethora of activities, undergo germinal centre reactions to ensure humoral immunity. With the recent approval for the addition of immunotherapeutic drugs as a treatment option in the early and metastatic settings for triple-negative breast cancer (TNBC) patients, B cell populations or TLS may resemble valuable biomarkers for immunotherapy responses in certain breast cancer subgroups. New technologies such as spatially defined sequencing techniques, multiplex imaging, and digital technologies have further deciphered the diversity of B cells and the morphological structures in which they appear in the tumour and LNs. Thus, in this review, we comprehensively summarise the current knowledge of B cells in breast cancer. In addition, we provide a user-friendly single-cell RNA-sequencing platform, called “B singLe cEll rna-Seq browSer” (BLESS) platform, with a focus on the B cells in breast cancer patients to interrogate the latest publicly available single-cell RNA-sequencing data collected from diverse breast cancer studies. Finally, we explore their clinical relevance as biomarkers or molecular targets for future interventions. Full article

(This article belongs to the Special Issue B Cells and Antibodies in Immune Surveillance and Therapy for Cancer)

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