CD40 stimulation via CD40 ligand enhances adenovirus-mediated tumour immunogenicity including 'find-me', 'eat-me', and 'kill-me' signalling.

Autor: Naseri S; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Cordova MM; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Wenthe J; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Lövgren T; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden., Eriksson E; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden.; Lokon Pharma AB, Uppsala, Sweden., Loskog A; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden.; Lokon Pharma AB, Uppsala, Sweden., Ullenhag GJ; Department of Immunology, Genetics and Pathology (IGP), Science for Life Laboratories, Uppsala University, Uppsala, Sweden.; Department of Oncology, Uppsala University Hospital, Uppsala, Sweden.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Apr; Vol. 28 (7), pp. e18162.
DOI: 10.1111/jcmm.18162
Abstrakt: 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.
(© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: