Role of inhibitory B cell co‐receptors in B cell self‐tolerance to non‐protein antigens*

Tsubata, Takeshi

doi:10.1111/imr.13059

Cited by 8 publications

(6 citation statements)

References 154 publications

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“…TLR7 (toll-like receptors 7) is an endosomal pattern recognition receptor, when activated, causes type I interferons and inflammatory reactions ( 57 ). TLR7 plays a crucial role in activating both natural and acquired immune responses and has an activating effect on virtually all cells engaged in the tumor immune response ( 58 ). Chemically coupling ibrutinib with TLR7 receptor agonists to produce novel immune-targeting complexes termed GY161 increased CD8 + T cell levels in spleen and tumor in vivo .…”

Section: Discussionmentioning

confidence: 99%

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Xing

Jia

et al. 2022

Front. Oncol.

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BackgroundCutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.MethodsWe analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, then used the LASSO COX regression model to develop a riskScore prognostic model, followed by a small molecule drug screening and molecular docking validation, which was then validated using qRT-PCR and IHC.ResultsWe developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. Multivariate Cox regression results indicated that riskScore is an independent and robust prognostic indicator, and its predictive value in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM.ConclusionsA riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model not only aids in predicting patient response to immunotherapy but also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.

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Section: Discussionmentioning

confidence: 99%

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Xing

Jia

et al. 2022

Front. Oncol.

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“…TLR7 (toll-like receptors 7) is an endosomal pattern recognition receptor, when activated, causes type I interferons and in ammatory reactions [49]. TLR7 plays a crucial role in activating both natural and acquired immune responses and has an activating effect on virtually all cells engaged in the tumor immune response [50]. It was discovered that chemically coupling ibrutinib with TLR7 receptor agonists to produce novel immune-targeting complexes called GY161 increased the levels of CD8 + T cells in spleen and tumor in vivo.…”

Section: Discussionmentioning

confidence: 99%

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Xing

Jia

Han

2022

Preprint

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Background Cutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation. Methods We analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, developed a riskScore prognostic model using the LASSO COX regression model, and performed small molecule drug screening and molecular docking validation, which was finally validated using qRT-PCR and IHC. Results We developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. The results of multivariate Cox regression demonstrated that riskScore is an independent and robust prognostic indicator, and its predictive usefulness in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM. Conclusions A riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model aid in predicting patient response to immunotherapy, but it also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.

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“…As described above, upon BCR ligation, Lyn phosphorylates ITIM motifs on several inhibitory co-receptors that regulate BCR signaling through SHP-1. Depending on the ligand recognized by these inhibitory receptors and their unique expression profiles, they regulate activation of different B cell subsets with specific BCRs [ 248 , 249 ].…”

Section: Other Signaling Pathways Implicated In Autoimmunitymentioning

confidence: 99%

Aberrant B Cell Signaling in Autoimmune Diseases

Corneth

Neys

Hendriks

2022

Cells

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Aberrant B cell signaling plays a critical in role in various systemic and organ-specific autoimmune diseases. This is supported by genetic evidence by many functional studies in B cells from patients or specific animal models and by the observed efficacy of small-molecule inhibitors. In this review, we first discuss key signal transduction pathways downstream of the B cell receptor (BCR) that ensure that autoreactive B cells are removed from the repertoire or functionally silenced. We provide an overview of aberrant BCR signaling that is associated with inappropriate B cell repertoire selection and activation or survival of peripheral B cell populations and plasma cells, finally leading to autoantibody formation. Next to BCR signaling, abnormalities in other signal transduction pathways have been implicated in autoimmune disease. These include reduced activity of several phosphates that are downstream of co-inhibitory receptors on B cells and increased levels of BAFF and APRIL, which support survival of B cells and plasma cells. Importantly, pathogenic synergy of the BCR and Toll-like receptors (TLR), which can be activated by endogenous ligands, such as self-nucleic acids, has been shown to enhance autoimmunity. Finally, we will briefly discuss therapeutic strategies for autoimmune disease based on interfering with signal transduction in B cells.

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Role of inhibitory B cell co‐receptors in B cell self‐tolerance to non‐protein antigens*

Cited by 8 publications

References 154 publications

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Aberrant B Cell Signaling in Autoimmune Diseases

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