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Published on: October 20, 2023
[Effects of Sema3A derived from tumor cells on functions of dendritic cells]
Xie-lai Zhou1, Yin Huang, Fang Wang
1Department of Basic Medicine, Hangzhou Normal University, Hangzhou 310036, China.
Objective:
To investigate the effects of tumor cell-derived Sema3A on the immunological functions of murine dendritic cells (DCs).
Methods:
Lung adenocarcinoma A549 cells were transfected with small interference RNA, Si-Sema and Si-mut, and the interference efficiency was determined by real-time PCR and Western-blot. The concentrated supernatants from cultured tumor cells, Si-Sema and Si-mut-infected tumor cells were subjected to DCs respectively. The immunophenotypes of DCs were analyzed by flow cytometry, the production of IL-12P70 and the ability of DCs to stimulate DO11. 10 T cells secreting IFN-gamma and IL-2 were detected by enzyme linked immunosorbent assay (ELISA).
Results:
Knockdown with Si-Sema3A significantly decreased the secretion of Sema3A by A549 cells in comparison with the Si-mut cells. DCs exposed to supernatants from Si-Sema cells showed elevated levels of MHC, CD40 and CD80, more production of IL-12P70, and enhanced capability of activating antigen-specific T cells, as evidenced by the remarkably increased levels of IFN-gamma and IL-2.
Conclusion:
A549 cells secrete Sema3A to inhibit the maturation and functions of DCs, which might be associated with the unidentified mechanism of immune evasion by tumor cells.
Insights
Tumor cells secrete Semaphorin 3A (Sema3A) to suppress dendritic cell (DC) maturation and function. Inhibiting Sema3A enhances DC immune responses, suggesting a role in tumor immune evasion.
Area of Science:
- Immunology
- Cancer Biology
- Cell Signaling
Context:
- Dendritic cells (DCs) are crucial for initiating adaptive immune responses.
- Tumor cells often employ mechanisms to evade immune surveillance.
- Semaphorin 3A (Sema3A) is implicated in various biological processes, including immune modulation.
Purpose:
- To investigate the impact of tumor cell-secreted Sema3A on murine dendritic cell (DC) immunological functions.
- To determine if Sema3A secreted by lung adenocarcinoma cells affects DC maturation and T cell activation.
Summary:
- Lung adenocarcinoma A549 cells were manipulated to alter Sema3A secretion using small interference RNA (Si-Sema3A).
- Supernatants from these cells were applied to DCs, and their immunophenotypes, IL-12P70 production, and T cell activation capabilities (IFN-gamma, IL-2 secretion) were assessed.
- Reduced Sema3A levels led to increased DC expression of MHC, CD40, CD80, enhanced IL-12P70 production, and improved activation of antigen-specific T cells.
Impact:
- Tumor-derived Sema3A actively inhibits DC maturation and function.
- This inhibition may represent a mechanism of immune evasion utilized by tumor cells.
- Targeting Sema3A could potentially enhance anti-tumor immunity.
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