Role of B cells as antigen presenting cells

Rastogi, Ichwaku; Jeon, Donghwan; Moseman, Jena E.; Muralidhar, Anusha; Potluri, Hemanth K; McNeel, Douglas G.

doi:10.3389/fimmu.2022.954936

Cited by 122 publications

(61 citation statements)

References 229 publications

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“…Furthermore, the spatial orientation of CD25 + T cells are on the margins and not in the cytolytic core, suggesting that NOS2/COX2 inhibition not only changes the immune tone but also the spatial arrangement of immune mediators. Importantly, this novel spatial orientation provides an opportunity for the T cells, CD11c + DC, and B cells to cross-train each other leading to a more positive therapeutic response [ 44 ]. A study describing an in situ vaccine utilizing an IL12 agent combined with radiation demonstrated that T cell-based antigen recognition along with humoral response through cross education was important for a stable resistance [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Nos2 Depletion and Cox inhibition limits TNBC disease progression and alters lymphoid cell spatial orientation and density

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Systemic Nos2 Depletion and Cox inhibition limits TNBC disease progression and alters lymphoid cell spatial orientation and density

et al. 2022

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“…The main function of B cells during tumorigenesis is their close relationship with T cells, allowing T cells to act against tumor cells. B cells act as antigen presenting cells to T cells [134][135][136][137]. B cells are also involved in secretion of anti-tumorigenic cytokines such as IFN-γ [134][135][136][137].…”

Section: T Cellsmentioning

confidence: 99%

“…B cells act as antigen presenting cells to T cells [134][135][136][137]. B cells are also involved in secretion of anti-tumorigenic cytokines such as IFN-γ [134][135][136][137]. However, several studies also show that B cells are pro-tumorigenic in some tumors [138][139][140].…”

Section: T Cellsmentioning

confidence: 99%

The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited

Dzobo¹,

Senthebane²,

Dandara³

2022

Preprint

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Tumorigenesis is a complex and dynamic process involving cell-cell and cell-extracellular matrix (ECM) interactions that allow tumor cell growth, drug resistance and metastasis. This review provides an updated summary of the role played by the tumor microenvironment (TME) components and hypoxia in tumorigenesis and highlight various ways through which tumor cells reprogram normal cells including into phenotypes that are pro-tumorigenic including cancer associated- fibroblasts, -macrophages and -endothelial cells. Tumor cells secrete numerous factors leading to transformation of a previously anti-tumorigenic environment into a pro-tumorigenic environment. Once formed, solid tumors continue to interact with various stromal cells including local and infiltrating fibroblasts, macrophages, mesenchymal stem cells, endothelial cells, pericytes, and secreted factors and the ECM within the tumor microenvironment (TME). The TME is key to tumorigenesis, drug response and treatment outcome. Importantly, stromal cells and secreted factors can initially be anti-tumorigenic but over time promote tumorigenesis and induce therapy resistance. To counter hypoxia, increased angiogenesis leads to formation of new vascular networks in order to actively promote and sustain tumor growth via supply of oxygen and nutrients whilst removing metabolic waste. Angiogenic vascular network formation aid in tumor cell metastatic dissemination. Successful tumor treatment and novel drug development require the identification and therapeutic targeting of pro-tumorigenic components of the TME including cancer-associated- fibroblasts (CAFs) and -macrophages (CAMs), hypoxia, blocking ECM-receptor interactions, in addition to targeting of tumor cells. Re-programming of stromal cells and the immune response to be anti-tumorigenic is key to therapeutic success. Lastly, this review highlights potential TME- and hypoxia-centred therapies under investigations.

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“…In addition to their essential role in the humoral immune response as antibody-secreting cells and by generating antibody-mediated memory responses, B cells are also capable of acting as professional APCs and thus play an important role in immune regulation and shaping of the evolving adaptive immune response (23). B cells are able to present antigens directly or by cross-presentation with enhanced capacity for antigen presentation in response to certain stimuli, comparable to that of DCs (24). Thus, they activate naive CD8 + T cells and promote robust CD4 + and CD8 + T-cell memory responses, while also playing a dominant role in recall responses (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

“…B cells are able to present antigens directly or by cross-presentation with enhanced capacity for antigen presentation in response to certain stimuli, comparable to that of DCs (24). Thus, they activate naive CD8 + T cells and promote robust CD4 + and CD8 + T-cell memory responses, while also playing a dominant role in recall responses (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Reinforcement of cell-mediated immunity driven by tumor-associated Epstein-Barr virus (EBV)-specific T cells during targeted B-cell therapy with rituximab

et al. 2023

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IntroductionIn immunocompromised patients, Epstein-Barr virus (EBV) infection or reactivation is associated with increased morbidity and mortality, including the development of B-cell lymphomas. The first-line treatment consists of reduction of immunosuppression and administration of rituximab (anti-CD20 antibody). Furthermore, the presence of EBV-specific T cells against latent EBV proteins is crucial for the control of EBV-associated diseases. Therefore, in addition to effective treatment strategies, appropriate monitoring of T cells of high-risk patients is of great importance for improving clinical outcome. In this study, we hypothesized that rituximab-mediated lysis of malignant EBV-infected B cells leads to the release and presentation of EBV-associated antigens and results in an augmentation of EBV-specific effector memory T-cell responses.MethodsEBV-infected B lymphoblastoid cell lines (B-LCLs) were used as a model for EBV-associated lymphomas, which are capable of expressing latency stage II and III EBV proteins present in all known EBV-positive malignant cells. Rituximab was administered to obtain cell lysates containing EBV antigens (ACEBV). Efficiency of cross-presentation of EBV-antigen by B-LCLs compared to cross-presentation by professional antigen presenting cells (APCs) such as dendritic cells (DCs) and B cells was investigated by in vitro T-cell immunoassays. Deep T-cell profiling of the tumor-reactive EBV-specific T cells in terms of activation, exhaustion, target cell killing, and cytokine profile was performed, assessing the expression of T-cell differentiation and activation markers as well as regulatory and cytotoxic molecules by interferon-γ (IFN-γ) EliSpot assay, multicolor flow cytometry, and multiplex analyses.ResultsBy inhibiting parts of the cross-presentation pathway, B-LCLs were shown to cross-present obtained exogenous ACEBV-derived antigens mainly through major histocompatibility complex (MHC) class I molecules. This mechanism is comparable to that for DCs and B cells and resulted in a strong EBV-specific CD8+ cytotoxic T-cell response. Stimulation with ACEBV-loaded APCs also led to the activation of CD4+ T helper cells, suggesting that longer peptide fragments are processed via the classical MHC class II pathway. In addition, B-LCLs were also found to be able to take up exogenous antigens from surrounding cells by endocytosis leading to induction of EBV-specific T-cell responses although to a much lesser extent than cross-presentation of ACEBV-derived antigens. Increased expression of activation markers CD25, CD71 and CD137 were detected on EBV-specific T cells stimulated with ACEBV-loaded APCs, which showed high proliferative and cytotoxic capacity as indicated by enhanced EBV-specific frequencies and increased secretion levels of cytotoxic effector molecules (e.g. IFN-γ, granzyme B, perforin, and granulysin). Expression of the regulatory proteins PD-1 and Tim-3 was induced but had no negative impact on effector T-cell functions.ConclusionIn this study, we showed for the first time that rituximab-mediated lysis of EBV-infected tumor cells can efficiently boost EBV-specific endogenous effector memory T-cell responses through cross-presentation of EBV-derived antigens. This promotes the restoration of antiviral cellular immunity and presents an efficient mechanism to improve the treatment of CD20+ EBV-associated malignancies. This effect is also conceivable for other therapeutic antibodies or even for therapeutically applied unmodified or genetically modified T cells, which lead to the release of tumor antigens after specific cell lysis.

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Role of B cells as antigen presenting cells

Cited by 122 publications

References 229 publications

Systemic Nos2 Depletion and Cox inhibition limits TNBC disease progression and alters lymphoid cell spatial orientation and density

Systemic Nos2 Depletion and Cox inhibition limits TNBC disease progression and alters lymphoid cell spatial orientation and density

The Tumor Microenvironment in Tumorigenesis and Therapy Resistance Revisited

Reinforcement of cell-mediated immunity driven by tumor-associated Epstein-Barr virus (EBV)-specific T cells during targeted B-cell therapy with rituximab

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