CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer

Wang, Binhan; Wang, Manni; Ao, Danyi; Wei, Xiawei

doi:10.1016/j.bbcan.2022.188799

Cited by 30 publications

(25 citation statements)

References 261 publications

(159 reference statements)

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“…These PD‐1 high CXCL13 + MAIT cells produce less IFN‐γ but more IL‐21 [84]. CXCL13 is the ligand of CXCR5, and the interaction between CXCR5 and CXCL13 leads to the activation of Tfh cells and their migration to the germinal centre of lymphoid organs, where they support the differentiation of B cells into antibody‐producing plasma cells [85]. These findings suggest that MAIT cells may regulate immune responses by promoting B cell activity.…”

Section: Mait Phenotype and Function In Gastrointestinal Cancermentioning

confidence: 99%

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

et al. 2023

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Mucosa‐associated invariant T cells (MAIT) are a class of innate‐like T lymphocytes mainly presenting CD8+ phenotype with a semi‐invariant αβ T‐cell receptor, which specifically recognises MR1‐presented biosynthetic derivatives of riboflavin synthesis produced by various types of microbiomes. As innate‐like T lymphocytes, MAIT can be activated by a variety of cytokines, leading to immediate immune responses to infection and tumour cues. As an organ that communicates with the external environment, the digestive tract, especially the gastrointestinal tract, contains abundant microbial populations. Communication between MAIT and local microbiomes is important for the homeostasis of mucosal immunity. In addition, accumulating evidence suggests changes in the abundance and structure of the microbial community during inflammation and tumorigenesis plays a critical role in disease progress partly through their impact on MAIT development and function. Therefore, it is essential for the understanding of MAIT response and their interaction with microbiomes in the digestive tract. Here, we summarised MAIT characteristics in the digestive tract and its alteration facing inflammation and tumour, raising that targeting MAIT can be a candidate for treatment of gastrointestinal diseases.

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Section: Mait Phenotype and Function In Gastrointestinal Cancermentioning

confidence: 99%

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

et al. 2023

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“…One salient example is the chemokine ligand CXCL13, which, in conjunction with its receptor CXCR5, orchestrates the immune milieu within the tumour 19 . This particular axis has broad implications, influencing the entire spectrum of tumourigenesis and determining the tumour's amenability to immunotherapeutic interventions 20,21 . This molecular interaction is instrumental in recruiting CXCR5‐expressing lymphocytes—most notably T cells—into the tumour.…”

Section: Introductionmentioning

confidence: 99%

“…19 This particular axis has broad implications, influencing the entire spectrum of tumourigenesis and determining the tumour's amenability to immunotherapeutic interventions. 20,21 This molecular interaction is instrumental in recruiting CXCR5-expressing lymphocytes-most notably T cells-into the tumour. This recruitment, in turn, could exert a modulatory effect on anti-tumour immune responses.…”

Section: Introductionmentioning

confidence: 99%

Unlocking PD‐1 antibody resistance: The MUC1 DNA vaccine augments CD8⁺ T cell infiltration and attenuates tumour suppression

Wang,

Miao,

Shen

et al. 2024

Scand J Immunol

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In light of increasing resistance to PD1 antibody therapy among certain patient populations, there is a critical need for in‐depth research. Our study assesses the synergistic effects of a MUC1 DNA vaccine and PD1 antibody for surmounting PD1 resistance, employing a murine CT26/MUC1 colon carcinoma model for this purpose. When given as a standalone treatment, PD1 antibodies showed no impact on tumour growth. Additionally, there was no change observed in the intra‐tumoural T‐cell ratios or in the functionality of T‐cells. In contrast, the sole administration of a MUC1 DNA vaccine markedly boosted the cytotoxicity of CD8+ T cells by elevating IFN‐γ and granzyme B production. Our compelling evidence highlights that combination therapy more effectively inhibited tumour growth and prolonged survival compared to either monotherapy, thus mitigating the limitations intrinsic to single‐agent therapies. This enhanced efficacy was driven by a significant alteration in the tumour microenvironment, skewing it towards pro‐immunogenic conditions. This assertion is backed by a raised CD8+/CD4+ T‐cell ratio and a decrease in immunosuppressive MDSC and Treg cell populations. On the mechanistic front, the synergistic therapy amplified expression levels of CXCL13 in tumours, subsequently facilitating T‐cell ingress into the tumour setting. In summary, our findings advocate for integrated therapy as a potent mechanism for surmounting PD1 antibody resistance, capitalizing on improved T‐cell functionality and infiltration. This investigation affords critical perspectives on enhancing anti‐tumour immunity through the application of innovative therapeutic strategies.

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“…Spatial proximity within B cell follicles allows highly specific and productive interactions of B cells and Tfh cells, along with the formation of GCs, the main sites of B cell proliferation, differentiation, BCR affinity maturation, and antibody production, resulting in the generation of memory B cells, long-lived plasma cells, and high-affinity antigen-specific IgG antibodies [ 16 , 26 ]. Tfh cells have a fundamental role in the function and maintenance of the humoral immune system [ 16 , 21 , 28 , 29 ]. In addition to B cells and Tfh cells, additional CXCR5+-expressing lymphocytes exist, e.g., T follicular regulatory cells (T FR ), natural killer T follicular helper (NK-Tfh) cells, follicular regulatory CD8+ T cells (CD8-Tfr), and follicular CD8+ T cells (Tf8).…”

Section: Introductionmentioning

confidence: 99%

Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research

Hoellwerth

Koelblinger

Lang

et al. 2023

Life

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CXCL13 is a potent chemoattractant cytokine that promotes the migration of cells expressing its cognate receptor, CXCR5. Accordingly, T follicular helper cells and B cells migrate towards B cell follicles in lymph nodes, where the resulting spatial proximity promotes B cell/T cell interaction and antibody formation. Moreover, effector cells of the CXCL13/CXCR5-associated immune axis express PD-1, with corresponding circulating cells occurring in the blood. The formation of so-called ectopic or tertiary lymphoid structures, recently detected in different cancer types, represents an integral part of this axis, particularly in the context of its emerging role in anti-tumor defense. These aspects of the CXCL13/CXCR5-associated immune axis are highlighted in this review, which focuses on cutaneous malignant melanoma. Specifically, we elaborate on the role of this important immune axis as a possible ancillary target of immune checkpoint inhibition with anti-PD-1 antibodies in different therapeutic settings and as a potential source of predictive biomarkers regarding treatment efficacy.

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CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer

Cited by 30 publications

References 261 publications

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

Unlocking PD‐1 antibody resistance: The MUC1 DNA vaccine augments CD8⁺ T cell infiltration and attenuates tumour suppression

Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research

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CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer

Cited by 30 publications

References 261 publications

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

Unlocking PD‐1 antibody resistance: The MUC1 DNA vaccine augments CD8+ T cell infiltration and attenuates tumour suppression

Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research

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Unlocking PD‐1 antibody resistance: The MUC1 DNA vaccine augments CD8⁺ T cell infiltration and attenuates tumour suppression