Viral infections lead to alarmin release and elicit potent cytotoxic effector
T lymphocyte (CTLeff) responses. Conversely, the induction of protective
tumour-specific CTLeff 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
CTLeff 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 CTLeff
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
