Co-expression of CD40/CD40L On XG1 Multiple Myeloma Cells Promotes IL-6 Autocrine Function

Qi, Chunjian; Tian, Shasha; Wang, Jiangfang; Ma, Hongbin; Qian, Keqing; Zhang, Xueguang

doi:10.3109/07357907.2014.988340

Cited by 8 publications

(4 citation statements)

References 34 publications

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“…Interactions between CD40/CD40L further amplify immune activation and cytokine release, implicating multiple cell types in CRS pathology. Additionally, CD40/CD40L interactions contribute to endothelial cell activation, further elucidating the complex mechanisms underlying CRS [51][52][53].…”

Section: Cytokine-release Syndrome (Crs)mentioning

confidence: 99%

The Future Directions of CAR-T Cell Therapy: Unlocking the Potential of Immunotherapy in Cancer Treatment

Justiz-Vaillant,

Soodeen,

Gopaul

et al. 2024

Preprint

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CAR-T cell therapy has emerged as a groundbreaking approach in cancer treatment, leveraging the immune system to target and eliminate cancer cells. While currently focused on hematologic malignancies, the future holds promise for expanding CAR-T cell therapy to diverse cancers, enhancing its efficacy, and improving safety profiles. Recent advances in tumor immunology have propelled CAR-T cell therapy as a game-changer in treating diseases such as relapsed/refractory B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). Six CAR-T cell products have received FDA approval for treating R/R B cell malignancies. However, challenges persist, including complications like cytokine release syndrome (CRS), coagulopathy, and cytopenias. Strategies to mitigate these complications involve targeting distinct antigens with dual- or multi-targeted CAR-T cells and enhancing immunogenicity. Additionally, γδ CAR-T cells show promise in recognizing antigen- negative leukemia cells in an MHC-independent manner while reducing the risk of inducing graft-versus-host disease (GVHD). As CAR-T cell therapy continues to evolve through innovation and discovery, it holds the potential to revolutionize cancer treatment, offering new hope to patients and reshaping the landscape of oncology with its precision and efficacy.

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Section: Cytokine-release Syndrome (Crs)mentioning

confidence: 99%

The Future Directions of CAR-T Cell Therapy: Unlocking the Potential of Immunotherapy in Cancer Treatment

Justiz-Vaillant,

Soodeen,

Gopaul

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Currently, it has been demonstrated that macrophages and monocytes rather than CAR-T cells are the major sources of these cytokines and contribute to CRS (91,92,102,103). In addition, the CD40 and CD40 ligand (CD40L) interactions between CAR-T cells and host antigen-presenting cells (APCs) as well as tumor cells also play an important role in immune activation and the release of cytokines (104)(105)(106). CD40 is expressed on multiple APCs, including B cells, macrophages, dendritic cells (DCs), and monocytes, and highly expressed in a variety of hematological malignancies, such as NHL, AML, MM (105)(106)(107)(108).…”

Section: Cytokine Release Syndromementioning

confidence: 99%

“…In addition, the CD40 and CD40 ligand (CD40L) interactions between CAR-T cells and host antigen-presenting cells (APCs) as well as tumor cells also play an important role in immune activation and the release of cytokines (104)(105)(106). CD40 is expressed on multiple APCs, including B cells, macrophages, dendritic cells (DCs), and monocytes, and highly expressed in a variety of hematological malignancies, such as NHL, AML, MM (105)(106)(107)(108). CD40L is highly expressed on activated T cells, including CAR-T cells (104,109).…”

Section: Cytokine Release Syndromementioning

confidence: 99%

CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges

et al. 2022

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Chimeric antigen receptor T (CAR-T) cell therapy represents a major breakthrough in cancer treatment, and it has achieved unprecedented success in hematological malignancies, especially in relapsed/refractory (R/R) B cell malignancies. At present, CD19 and BCMA are the most common targets in CAR-T cell therapy, and numerous novel therapeutic targets are being explored. However, the adverse events related to CAR-T cell therapy might be serious or even life-threatening, such as cytokine release syndrome (CRS), CAR-T-cell-related encephalopathy syndrome (CRES), infections, cytopenia, and CRS-related coagulopathy. In addition, due to antigen escape, the limited CAR-T cell persistence, and immunosuppressive tumor microenvironment, a considerable proportion of patients relapse after CAR-T cell therapy. Thus, in this review, we focus on the progress and challenges of CAR-T cell therapy in hematological malignancies, such as attractive therapeutic targets, CAR-T related toxicities, and resistance to CAR-T cell therapy, and provide some practical recommendations.

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“…Numerous molecules and cytokines can upregulate the secretion of IL-6 derived from BMSCs. It has been previously reported that IL-6 can be detected in the supernatant of MM cells using stimulation with anti-CD40 antibody (69,70). Additionally, IL-1β has also been indicated to be a major cytokine that contributes to the production of BMSC IL-6 via the paracrine loop, which promotes the growth and survival of MM cells (71).…”

Section: The Bone Marrow Microenvironmentmentioning

confidence: 99%

The impact of the bone marrow microenvironment on multiple myeloma (Review)

et al. 2019

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Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells in the bone marrow (BM). The interaction between the BM microenvironment and MM plasma cells can influence cell proliferation, drug resistance and prognosis of the disease. The BM microenvironment (BMME) consists of a cellular and non-cellular compartment. The cellular compartment includes stromal cells, endothelial cells, osteoclasts and osteoblasts, and the non-cellular compartment includes the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors and chemokines. The complex interaction between the BM microenvironment and MM plasma cells influences disease development and prognosis. The present review focuses on the interaction between malignant plasma cells and the BM microenvironment during MM progression. An improved understanding of the interaction between MM plasma cells and their microenvironment will enable the development of novel therapeutic tools that can be used in the treatment of MM, a currently incurable blood cancer. Contents 1. Introduction 2. The bone marrow microenvironment 3. Conclusion

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Co-expression of CD40/CD40L On XG1 Multiple Myeloma Cells Promotes IL-6 Autocrine Function

Cited by 8 publications

References 34 publications

The Future Directions of CAR-T Cell Therapy: Unlocking the Potential of Immunotherapy in Cancer Treatment

The Future Directions of CAR-T Cell Therapy: Unlocking the Potential of Immunotherapy in Cancer Treatment

CAR-T Cell Therapy in Hematological Malignancies: Current Opportunities and Challenges

The impact of the bone marrow microenvironment on multiple myeloma (Review)

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