Resumen
The efficacy of some cancer chemotherapies relies on their ability to induce immunogenic cell death (ICD) to activate the immune system. In addition, it has been suggested that treatments that provoke ICD could be used in combination with chemotherapies to improve their anti-cancer actions. Having determined that mutating the caspase cleavage site in ROCK1 promoted necrosis-like inflammatory cell death during acute chemically induced liver damage and in hepatocellular carcinomas, we examined whether similar effects would be induced by pharmacological ROCK inhibition. Although mice expressing the caspase-resistant non-cleavable ROCK1 (ROCK1nc) had higher levels of neutrophils and CD8+ T cells in hepatocellular carcinoma tumours than in ROCK1 wild-type mice, indicative of greater ICD, two independent pharmacological ROCK inhibitors did not induce similar patterns. As a result, there is unlikely to be a clinical benefit derived from using pharmacological ROCK inhibitors to provoke ICD with standard of care therapies to increase their therapeutic efficacy.