Abstract
Lycium barbarum polysaccharide (LBP) is the major function component of Lycium barbarum L. and has been previously reported to induce the phenotypic and functional maturation of dendritic cells (DCs) as well as activating T lymphocytes. In the current study, the immunologic cytotoxicity promoting effect of LBP was assessed and the underlying mechanism was explored. The impact of LBP on the phenotype, maturation, and immunogenicity of DCs was assessed. The activity of Notch pathway which is involved in the regulation of LBP on DCs was detected. Afterwards, the influence of LBP on cytotoxicity of DC-mediated cytotoxicity T lymphocytes (CTLs) to CT26-WT colon cancer cells was further assessed. Administration of LBP induced the phenotypic and functional maturation of DCs. After being subjected to LBP, the expression of Notch and Jagged and Notch targets Hes1 and Hes5 was all upregulated. The cytotoxicity of DC-mediated CTLs was strengthened by administration of LBP. Additionally, cytotoxicity of DC-mediated CTLs on CT26-WT colon cancer cells also increased with effector-target ratio. In conclusion, LBP could induce the phenotypic and functional maturation of DCs via Notch signaling and promote the cytotoxicity of DC-mediated CTLs, which could be employed as a promising adjuvant for cancer immunotherapy.
Highlights
The concept of immune contexture is mainly emerged based on studies that are mostly performed with human colorectal cancer (CRC) [1]
It is commonly recognized that functioning of an effective immunotherapy majorly depends on the roles of immune cells playing in the development of tumors, especially those with antigen presentation capability, that is, dendritic cells (DCs) [8], and those with cytolytic activity, that is, cytotoxicity T lymphocytes (CTLs) [9]
Findings outlined in the current study showed that administration of Lycium barbarum polysaccharide (LBP) promoted the maturation and immunogenicity of DCs via Notch signaling, which strengthened the cytotoxicity of DC-mediated CTLs to tumor cells
Summary
The concept of immune contexture is mainly emerged based on studies that are mostly performed with human colorectal cancer (CRC) [1]. Study of Pages et al showed that high density of intratumoral memory T cells was closely associated with the disease free time and overall survival rate of CRC patients [2]. In addition to the findings in CRC, Becht and his colleagues proved the beneficial effect of high densities of T cells with a Th1 orientation and of cytotoxic CD8+ T cells in non-small cell lung cancer (NSCLC) [3, 4]. The immune system can prevent the development and progression of cancer through a mechanism called immune surveillance.
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