Rate of Freeze Alters the Immunologic Response After Cryoablation of Breast Cancer

Abstract

Cryoablation has garnered significant interest as a treatment for solid tumors including breast cancer for both its local effects and potential in stimulating an antitumor immune response. We sought to examine the impact that variances in technique might have on the immune response and examine the mechanism by which cryoablation may stimulate an antitumor immune response. Balb/c mice with established 4T1 mammary carcinomas were treated by cryoablation at either a high rate of freeze or low rate of freeze, or by surgical excision, after spontaneous metastases occurred. Tumor-draining lymph nodes (TDLN) were excised at 1 week for EliSPOT assay and immunophenotyping. Mice were followed after treatment for enumeration of pulmonary metastases and survival. Compared with surgical excision, cryoablation using a high freeze rate resulted in a significant increase in tumor-specific T cells in the TDLN, a reduction in pulmonary metastases, and improved survival. However, cryoablation using a low freeze rate resulted in an increase in regulatory T cells, a significant increase in pulmonary metastases, and decreased survival. Cryoablation of breast cancer in mice can generate a tumor-specific immune response that can eradicate systemic micrometastases and improve outcome compared with surgical excision; however, the technique used to freeze the tissue may alter the immune response from stimulatory to suppressive.