Absin multicolor kits help cervical cancer research

This article published in Cancer Communications titled "Interactions of Indoleamine 2,3-dioxygenase-expressing LAMP3+ dendritic cells with CD4+ regulatory T cells and CD8+ exhausted T cells: synergistically." remodeling of the immunosuppressive microenvironment in cervical cancer and therapeutic implications is a study of the immune microenvironment of cervical cancer, with a particular focus on LAMP3+ dendritic cells (DCs) and CD4+ regulatory T cells (Tregs) and CD8+ depleting T cells (Tex) and how these interactions synergistically reshape the immunosuppressive microenvironment in cervical cancer and explore therapeutic implications.
Background:
Cervical cancer is the fourth most common cancer in women worldwide, and although immunotherapy has been used in clinical practice, its efficacy is not ideal. Therefore, researchers need to further explore the mechanism of immune remodeling in cervical cancer and explore new therapeutic targets.
Research Methods:
● Single-cell RNA sequencing (scRNA-seq): Single-cell RNA sequencing was performed on 17 clinical samples, including normal cervical tissue, high-grade squamous intraepithelial lesions, and cervical cancer tissues, to explore cell subsets and interactions within the tumor immune microenvironment (TME).
● Multicolor immunohistochemical staining (mIHC): In order to verify the discovery of scRNA-seq, the researchers performed multicolor mIHC staining on cervical cancer tissues to observe the spatial colocalization of LAMP3+ DCs with CD4+ Tregs and CD8+ Tex cells.
Indicator interpretation
● LAMP3+ dendritic cells (DCs):LAMP3 is a lysosome-associated membrane protein that is commonly expressed in mature DCs. The study in the article shows that these cells express IDO1 (indoleamine 2,3-dioxygenase) in cervical cancer, which is involved in tryptophan metabolism and is associated with immunosuppression.
● CD4+ regulatory T cells (Tregs): These cells regulate the immune response by expressing marker genes such as FOXP3, often playing a role in inhibiting excessive immune activation. It is mentioned in the article that the interaction of Tregs with LAMP3+ DCs may promote immune escape in cervical cancer.
● CD8+ depleted T cells (Tex): These cells are functionally depleted CD8+ T cells that typically emerge under long-term antigen stimulation and manifest as high expression of PD-1. The data in the article suggest that the interaction of these cells with LAMP3+ DCs may contribute to the formation of an immunosuppressive microenvironment.
● Mouse model experiments: A subcutaneous tumor model of C57BL/6 mice was constructed, and the effect of combination treatment with IDO1 inhibitor and immune checkpoint blockade (ICB) was evaluated using a mouse cervical cancer cell line (TC1).
Findings:
● Characteristics of LAMP3+ DCs: Studies have found that LAMP3+ DCs express IDO1 in a mature state, affect tryptophan metabolism, and interact with tumor reactive depleted CD8+ T cells and CD4+ regulatory T cells to form an immunosuppressive cycle and mediate the immune escape of cervical cancer.
● Multicolor mIHC results: The colocalization of neoantigen-reactive T cells (CD3+, CD4+/CD8+, and PD-1+) and LAMP3+ DCs (CD80+ and PD-L1+) in the cervical cancer microenvironment was verified by multicolor mIHC.
● Effect of combination therapy: In mouse models, the combination of IDO1 inhibitor and ICB significantly reduced tumor volume compared with ICB alone.
conclusion
In summary, the role of LAMP3+ DCs in cervical cancer is multifaceted, they are not only involved in the immunomodulation and metabolic processes in the tumor microenvironment, but also closely related to the interaction between tumor cells and T cells, and jointly promote the immune escape and progression of tumors. Therefore, LAMP3+ DCs can be considered as potential targets for immunotherapy of cervical cancer.
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