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CD40 stimulation vi...
CD40 stimulation via CD40 ligand enhances adenovirus-mediated tumour immunogenicity including 'find-me', 'eat-me', and 'kill-me' signalling
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- Naseri, Sedigheh (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerimmunterapi
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- Mejia Cordova, Mariela (författare)
- Uppsala universitet,Cancerimmunterapi,Science for Life Laboratory, SciLifeLab
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- Wenthe, Jessica (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerimmunterapi
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- Lövgren, Tanja (författare)
- Uppsala universitet,Cancerimmunterapi,Science for Life Laboratory, SciLifeLab
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- Eriksson, Emma (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerimmunterapi,Lokon Pharm AB, Uppsala, Sweden
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- Loskog, Angelica, 1973- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerimmunterapi,Lokon Pharm AB, Uppsala, Sweden
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- Ullenhag, Gustav J. (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Cancerimmunterapi,Uppsala Univ Hosp, Dept Oncol, Uppsala, Sweden
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(creator_code:org_t)
- John Wiley & Sons, 2024
- 2024
- Engelska.
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Ingår i: Journal of Cellular and Molecular Medicine (Print). - : John Wiley & Sons. - 1582-1838 .- 1582-4934. ; 28:7
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Immunostimulatory gene therapy using oncolytic viruses is currently evaluated as a promising therapy for cancer aiming to induce anti-tumour immunity. Here, we investigate the capacity of oncolytic adenoviruses (LOAd) and their transgenes to induce immunogenicity in the infected tumour cells. Oncolysis and death-related markers were assessed after infection of eight human solid cancer cell lines with different LOAd viruses expressing a trimerized, membrane-bound (TMZ)-CD40L, TMZ-CD40L and 41BBL, or no transgenes. The viruses induced transgene expression post infection before they were killed by oncolysis. Death receptors TRAIL-R1, TRAIL-R2 and Fas as well as immunogenic cell death marker calreticulin were upregulated in cell lines post infection. Similarly, caspase 3/7 activity was increased in most cell lines. Interestingly, in CD40+ cell lines there was a significant effect of the TMZ-CD40L-encoding viruses indicating activation of the CD40-mediated apoptosis pathway. Further, these cell lines showed a significant increase of calreticulin, and TRAIL receptor 1 and 2 post infection. However, LOAd viruses induced PD-L1 upregulation which may hamper anti-tumour immune responses. In conclusion, LOAd infection increased the immunogenicity of infected tumour cells and this was potentiated by CD40 stimulation. Due to the simultaneous PD-L1 increase, LOAd viruses may benefit from combination with antibodies blocking PD1/PD-L1.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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