Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy.
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26 mai 2017
- doi: 10.1038/ncomms15327
- issn: 2041-1723
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S.M. Kallert et al., « Replicating viral vector platform exploits alarmin signals for potent CD8+ T cell-mediated tumour immunotherapy. », Serveur académique Lausannois, ID : 10.1038/ncomms15327
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Viral infections lead to alarmin release and elicit potent cytotoxic effector T lymphocyte (CTL eff ) responses. Conversely, the induction of protective tumour-specific CTL eff and their recruitment into the tumour remain challenging tasks. Here we show that lymphocytic choriomeningitis virus (LCMV) can be engineered to serve as a replication competent, stably-attenuated immunotherapy vector (artLCMV). artLCMV delivers tumour-associated antigens to dendritic cells for efficient CTL priming. Unlike replication-deficient vectors, artLCMV targets also lymphoid tissue stroma cells expressing the alarmin interleukin-33. By triggering interleukin-33 signals, artLCMV elicits CTL eff responses of higher magnitude and functionality than those induced by replication-deficient vectors. Superior anti-tumour efficacy of artLCMV immunotherapy depends on interleukin-33 signalling, and a massive CTL eff influx triggers an inflammatory conversion of the tumour microenvironment. Our observations suggest that replicating viral delivery systems can release alarmins for improved anti-tumour efficacy. These mechanistic insights may outweigh safety concerns around replicating viral vectors in cancer immunotherapy.