Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy. In this study, we used P815 mouse mastocytoma tumor model and immunized them with P815AB peptide and/or ICA. Our results demonstrated that ICA could increase the cytotoxic T lymphocytes (CTL) response for P815AB peptide on the tumor-bearing DBA/2J mice. In addition, the percentage of CD4CD8/CD3CD69/CD69NKG2D positive cells in splenocytes of the tumor-bearing mice all significantly increased after combined immunization with ICA and P815AB peptide. This illustrated that ICA could enhance the immunogenicity of P815AB and improve the ability of T cells and CTLs in recognizing the tumor cells. Moreover, ICA improved the function of peritoneal macrophages with effects of inhibition on tumor growth. Besides, we discussed the possible mechanism of ICA to enhance body immunity by detecting the expression level of MHC-I and related genes in B16-F10 and RMA/S cells. The results suggested that ICA has the potential to up-regulate LMP/TAP related molecules and induce the expression of MHC-I, which increase the immune surveillance and keep cancer in remission. In conclusion, ICA showed an anti-tumor effect both in vitro and in vivo and may be an effective antigen adjuvant for cancer treatment by enhancing tumor-specific immunity.
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http://dx.doi.org/10.1016/j.biopha.2018.01.139 | DOI Listing |
Biomed Pharmacother
March 2018
College of Animal Science, Jilin University, Changchun 130062, China. Electronic address:
Cancer immunotherapy has attracted much attention in recent years because of the ability of immune system to identify tumor cells and limit their growth. Icariin (ICA) is a natural flavonoid glucoside isolated from Epimedium plants and has shown a variety of pharmacological activities such as anti-inflammatory effects, immunological regulation and anticancer potency. Furthermore, it has immunoadjuvant effects on enhancing Th1-immune response, suggesting that ICA may serve as an adjuvant for cancer immunotherapy.
View Article and Find Full Text PDFJ Immunol
July 2001
Department of Experimental Medicine, University of Perugia, Via del Giochetto, I-06122 Perugia, Italy.
The outcome of dendritic cell (DC) presentation of tumor and/or self peptides, including P815AB (a tumor peptide of murine mastocytoma cells) and NRP-A7 (a synthetic peptide mimotope recognized by diabetogenic T cells), may depend on a balance between the activities of immunogenic (CD8alpha(-)) and tolerogenic (CD8alpha(+)) DC. By virtue of their respective actions on CD8(-) and CD8(+) DC, IL-12 and IFN-gamma have functionally opposing effects on peptide presentation by the CD8(-) DC subset, and IFN-gamma-activated CD8(+) DC mediate tolerogenic effects that prevail over the adjuvant activity of IL-12 on CD8(-) DC. We have previously shown that CD40 ligation abrogates the tolerogenic potential of CD8(+) DC, an effect associated with an impaired capacity of the CD40-modulated and IFN-gamma-treated DC to degrade tryptophan and initiate T cell apoptosis in vitro.
View Article and Find Full Text PDFJ Immunol
January 2001
Department of Experimental Medicine, University of Perugia, Perugia, Italy.
The outcome of dendritic cell (DC) presentation of P815AB, a tolerogenic tumor/self peptide, depends on a balance between the respective immunogenic and tolerogenic properties of myeloid (CD8 alpha(-)) and lymphoid (CD8 alpha(+)) DC. We have previously shown that CD8(-) DC can be primed by IL-12 to overcome inhibition by the CD8(+) subset and initiate immunogenic presentation in vivo when the two types of peptide-pulsed DC are cotransferred into recipient hosts. IFN-gamma enhances the inhibitory activity of CD8(+) DC on Ag presentation by the other subset, blocking the ability of IL-12-treated CD8(-) DC to overcome suppression.
View Article and Find Full Text PDFJ Immunol
November 2000
Department of Experimental Medicine, University of Perugia, Perugia, Italy.
Although CD8(+) T cells play a central role as immune effectors, CD4(+) T cells act to control the activation and persistence of the CD8(+) T cell response in autoimmune disease, antiviral immunity, and experimental systems with immunogenic model tumor Ag. However, little information is available on the effects of CD4(+) T cells on the function of endogenous CD8(+) T lymphocytes recognizing authentic tumor rejection Ag with limited immunogenicity. We report here that the prophylactic or postchallenge administration of T helper Th1-type and Th2-type CD4(+) clones specific for an unmutated rejection Ag (murine P815AB, resembling tumor-specific shared Ag in humans) leads to the induction of P815AB-specific reactivity in vivo and concomitant tumor destruction, with quantitative rather than qualitative differences characterizing the antitumor activity of Th1 vs Th2 cells.
View Article and Find Full Text PDFCancer Immunol Immunother
July 1999
Department of Experimental Medicine, University of Perugia, Giochetto, Italy.
Nonameric P815AB, a cytotoxic-T-lymphocyte-defined minimal core peptide encoded by the murine mastocytoma gene P1A, fails to initiate CD4+ cell-dependent reactivity in vivo to class-I-restricted epitopes when mice are administered peptide-pulsed dendritic cells. Effective immunization requires T helper effects, such as those mediated by coimmunization with class-II-restricted (helper) peptides or by the use of recombinant interleukin-12 (rIL-12). Although P815AB does possess class-II-restricted epitopes, they are likely suboptimal, resulting in poor affinity and/or stability of MHC/P815AB complexes and inadequate activation of the antigen-presenting cell function of dendritic cells.
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