Tumor stimulator cell modification by infection with Newcastle Disease Virus: analysis of effects and mechanism in MLTC-CML cultures
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Published on: February 11, 2015
V Schirrmacher1, K Jurianz, C Roth
1Abteilung Zellulare Immunologie (G0100), DKFZ, D-69120 Heidelberg, Germany.
Abstract:
Effects of tumor stimulator cell modification by infection with Newcastle Disease Virus (NDV) are described as analysed in vitro in mixed lymphocyte tumor cell cultures (MLTC). Direct antitumor effects were seen with human melanoma or colon-carcinoma cells in a dose- and time-dependent manner when using live but not UV inactivated virus. When T cell stimulation was measured by [3H]-thymidine uptake, NDV infected tumor stimulator cells did not show an augmentation but rather an inhibitory effect in comparison to non-infected stimulator cells. Virus infected tumor stimulator cells were, however, capable of augmenting the induction of tumor specific cytotoxic T cells in MLTC-CML assays when using murine ESb lymphoma immune cells and syngeneic NDV modified ESb cells as stimulators. A CML stimulatory effect was also shown for NDV modified third party cells and thereof derived conditioned medium. These effects are most likely explained by interferon- which is induced in tumor cells by NDV infection and by interferon-á which is induced in responder cells when stimulated with NDV infected stimulator cells.
Insights
Newcastle Disease Virus (NDV) can directly kill human cancer cells. However, NDV-infected cells inhibit T cell responses, but can enhance the induction of tumor-specific cytotoxic T cells, likely via interferon production.
Area of Science:
- Immunology
- Virology
- Oncology
Background:
- Newcastle Disease Virus (NDV) is an oncolytic virus with potential antitumor applications.
- Tumor stimulator cells are crucial for initiating immune responses against cancer.
- Understanding how viral modification of tumor cells impacts immune responses is vital for cancer immunotherapy.
Purpose of the Study:
- To investigate the effects of modifying tumor stimulator cells with NDV on antitumor immunity in vitro.
- To analyze the direct and indirect effects of NDV-infected tumor cells on T cell stimulation and cytotoxic T cell induction.
Main Methods:
- In vitro analysis using mixed lymphocyte tumor cell cultures (MLTC).
- Assays included direct cytotoxicity, [3H]-thymidine uptake for T cell stimulation, and MLTC-CML assays for cytotoxic T cell induction.
- Used human melanoma/colon-carcinoma cells and murine ESb lymphoma cells, infected with live or UV-inactivated NDV.
Main Results:
- Live NDV demonstrated direct dose- and time-dependent antitumor effects on human cancer cells.
- NDV-infected tumor stimulator cells inhibited T cell proliferation but augmented the induction of tumor-specific cytotoxic T cells.
- NDV-modified third-party cells and their conditioned medium also showed a cytotoxic T cell-stimulating effect.
Conclusions:
- NDV infection of tumor cells can elicit direct oncolysis and modulate immune responses.
- The observed effects are likely mediated by interferon-alpha induced in tumor cells and responder cells.
- NDV-modified tumor cells hold potential for enhancing anti-tumor cytotoxic T cell responses in cancer immunotherapy.
