Cryoablation of primary triple-negative breast cancer alters the tumor immune micro-environment in distant tumors.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B141
Abstract ID: 5933

Presenting Author:
Flavia Sardela de Miranda , Research Assistant at Texas Tech Univ. Hlth. Sci. Ctr.

Abstract:

Cryoablation induces tumor necrosis by freeze-thaw cycles while preserving cancer antigens for an adaptive immune response. Pre-clinical data found cryoablation of primary breast cancer (BC) resulted in lower rates of tumor recurrence and metastasis compared to resection. Identifying the mechanisms and biomarkers for clinical translation is needed. Using a murine model of triple-negative BC, we evaluated the immune response following cryoablation. 4T1-12B cells were bilaterally transplanted into BALB/c mice. At two weeks, left tumors were cryoablated (remained in mouse) or resected. Right (abscopal) tumors were collected a week later and immune response analyzed. Flow cytometry analysis did not show differences between abscopal tumors from resection and cryoablation. RNA-seq analysis revealed cryoablation had upregulation of gene expression associated with T and B cells in abscopal tumors. IPA pathway analysis showed decreased expression of genes associated with tumor promotion (Cx3cr1) and increased gene expression for tumor suppression (Stat6 and Nlrp12) and T cell cytotoxicity (Prf1). Spatial immune profiling using IHC tended to show increased intra-tumoral T cells and IFN-γ compared to resection in abscopal tumors. Our findings suggest cryoablation induces a systemic effect reducing immunosuppression while promoting infiltration of T-cells compared to resection in distant tumors. These findings may serve as biomarkers for predicting cryoablation efficacy.