Intratumoral inoculation of viruses with
tumor-selective cytotoxicity may induce
cancer cell death and, thereby, shrink neoplastic lesions. It is unlikely, however, that viral
tumor cell killing alone could produce meaningful, durable clinical responses, as clinically suitable 'oncolytic' viruses are severely attenuated and their spread and propagation are opposed by host immunity. Thus, a more propitious event in this context is the innate
antiviral response to intratumoral virus administration, in particular for recruiting durable adaptive immune effector responses. It may represent a double-edged sword, as innate immune activation may eliminate infected
tumor cells early, intercept viral spread and block any meaningful therapeutic response. The innate response to
viral infection of
tumors may be very different from that in non-malignant target tissues, owing to the unusual composition/tissue properties of
tumor stroma. In this work, we report investigations of the innate immune response to the oncolytic poliovirus recombinant, PVSRIPO, in two mouse
xenotransplantation models for breast and
prostate cancer. Our observations indicate short-term virus persistence in infected
tumors and virus recovery indicative of modest intratumoral propagation and persistence. Yet, a powerful
innate inflammatory response coincided with
chemokine induction and myeloid cell infiltration into
tumors that was, interestingly, dominated by neutrophils. The combined effect of PVSRIPO
tumor infection and the innate response it elicits was significant
tumor regression in both models.