Background: Moderate-to-severe acne vulgaris, which is a chronic inflammatory skin disease, seriously impacts millions of people. However, traditional therapies may cause severe adverse reactions that are unacceptable to many patients, thus limiting the further application of these therapies. Novel therapeutic approaches to effectively treat moderate-to-severe acne vulgaris with minimal adverse reactions are urgently needed.
View Article and Find Full Text PDFImmunotherapies are mainly aimed to promote a CD8 T cell response rather than a CD4 T cell response as cytotoxic T lymphocytes (CTLs) can directly kill target cells. Recently, CD4 T cells have received more attention due to their diverse roles in tumors and chronic viral infections. In antitumor and antichronic viral responses, CD4 T cells relay help signals through dendritic cells to indirectly regulate CD8 T cell response, interact with B cells or macrophages to indirectly modulate humoral immunity or macrophage polarization, and inhibit tumor blood vessel formation.
View Article and Find Full Text PDFJ Cancer Res Clin Oncol
December 2023
Background: Previously, albendazole (ABZ) has been reported as an anti-parasitic drug rather than anti-tumor drug. Our study aim to investigate whether ABZ also has a potential anti-tumor effect by shaping the tumor immune microenvironment and interrogate whether ABZ could synergize with the PD-L1 blockade.
Methods: C57BL/6 mice (C57) were intravenously injected with B16F10-luciferase (B16-luc) cells to establish a lung metastatic melanoma model and subcutaneously inoculated with B16-luc cells to establish a subcutaneous tumor model.
Follicular helper T (T) cells provide specialized help for B cells to ensure optimal humoral immunity. The histone methyltransferase EZH2, as a chromatin repressor, secures the T differentiation by promoting T lineage associated gene expression during acute viral infection, including and . By using conditional deletion murine system, we observed that EZH2 ablation in CD4 T cells was accompanied by aberrant accumulation of DNA methyltransferases (DNMTs) DNMT1 and DNMT3B in T cells.
View Article and Find Full Text PDFBackground: Antitumor therapeutic vaccines are generally based on antigenic epitopes presented by major histocompatibility complex (MHC-I) molecules to induce tumor-specific CD8 T cells. Paradoxically, continuous T cell receptor (TCR) stimulation from tumor-derived CD8 T-cell epitopes can drive the functional exhaustion of tumor-specific CD8 T cells. Tumor-specific type-I helper CD4 T (T1) cells play an important role in the population maintenance and cytotoxic function of exhausted tumor-specific CD8 T cells in the tumor microenvironment.
View Article and Find Full Text PDFAlbendazole (ABZ) is an effective broad-spectrum anthelmintic agent that has been widely used for humans and animals. Previous studies have reported that ABZ exhibits antitumor effects against melanoma and other different cancer types; however, it is unknown whether ABZ exerts the inhibitory effect against melanoma metastasis. In this study, we aimed to investigate the inhibitory effect of ABZ on melanoma cells.
View Article and Find Full Text PDFT cell-mediated immunity plays a crucial role in immune responses against tumors, with cytotoxic T lymphocytes (CTLs) playing the leading role in eradicating cancerous cells. However, the origins and replenishment of tumor antigen-specific CD8 T cells within the tumor microenvironment (TME) remain obscure. This protocol employs the B16F10-OVA melanoma cell line, which stably expresses the surrogate neoantigen, ovalbumin (OVA), and TCR transgenic OT-I mice, in which over 90% of CD8 T cells specifically recognize the OVA-derived peptide OVA257-264 (SIINFEKL) bound to the class I major histocompatibility complex (MHC) molecule H2-K.
View Article and Find Full Text PDFDuring tumorigenesis, tumor infiltrating regulatory T (Treg) cells restrict the function of effector T cells in tumor microenvironment and thereby promoting tumor growth. The anti-tumor activity of effector T cells can be therapeutically unleashed, and is now being exploited for the treatment of various types of human cancers. However, the immune suppressive function of Treg cells remains a major hurdle to broader effectiveness of tumor immunotherapy.
View Article and Find Full Text PDFFollicular helper T cells (TFH cells), known as the primary "helpers" of the germinal center (GC) reaction, promote the humoral immune response to defend against various pathogens. Under conditions of infection by different types of pathogens, many shared transcription factors (TFs), such as Bcl-6, TCF-1, and Maf, are selectively enriched in pathogen-specific TFH cells, orchestrating TFH cell differentiation and function. In addition, TFH cells also coexpress environmentally associated TFs as their conventional T cell counterparts (such as T-bet, GATA-3, or ROR-γt, which are expressed in Th1, Th2, or Th17 cells, respectively).
View Article and Find Full Text PDFEpigenetic modifications to histones dictate the differentiation of naïve CD4 T cells into different subsets of effector T helper (T) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T1, T2 and regulatory T (T) cells. However, whether and how EZH2 regulates follicular helper T (T) cell differentiation remain unknown.
View Article and Find Full Text PDFTo investigate the construction of the histological section datasets in the basal ganglia of digitized human brain to provide a reference for the meso-level histological data acquisition. A fresh adult brain from a cadaver with no neurological disease was selected, and tissue blocks of the basal ganglia in the right hemisphere was extracted using the visualization method, followed by pretreatments including gradient dehydrating, gelatin-embedding and setting of calibration points. And then the tissue blocks was cryosectioned into 60-μm-thick coronal sections and the sectional images were captured simultaneously by a digital camera at a fixed position.
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