Percutaneous
cryoablation is a minimally invasive procedure for
tumor destruction, which can potentially initiate or amplify antitumor immunity through the release of
tumor-associated
antigens. However, clinically efficacious immunity is lacking and regional recurrences are a limiting factor relative to surgical excision. To understand the mechanism of immune activation by
cryoablation, comprehensive analyses of innate immunity and HER2/neu humoral and cellular immunity following
cryoablation with or without peritumoral CpG injection were conducted using two HER2/neu(+)
tumor systems in wild-type (WT), neu-tolerant, and SCID mice.
Cryoablation of neu(+) TUBO
tumor in BALB/c mice resulted in systemic immune priming, but not in neu-tolerant BALB NeuT mice.
Cryoablation of human HER2(+) D2F2/E2
tumor enabled the functionality of
tumor-induced immunity, but secondary
tumors were refractory to antitumor immunity if rechallenge occurred during the resolution phase of the cryoablated
tumor. A step-wise increase in local recurrence was observed in WT, neu-tolerant, and SCID mice, indicating a role of adaptive immunity in controlling
residual tumor foci. Importantly, local recurrences were eliminated or greatly reduced in WT, neu tolerant, and SCID mice when CpG was incorporated in the
cryoablation regimen, showing significant local control by innate immunity. For long-term protection, however, adaptive immunity was required because most SCID mice eventually succumbed to local
tumor recurrence even with combined
cryoablation and CpG treatment. This improved understanding of the mechanisms by which
cryoablation affects innate and adaptive immunity will help guide appropriate combination of therapeutic interventions to improve treatment outcomes.