Immune Adjuvant Activity of Pre-Resectional Radiofrequency Ablation Protects against Local and Systemic Recurrence in Aggressive Murine Colorectal Cancer
Primary tumor
DOI:
10.1371/journal.pone.0143370
Publication Date:
2015-11-24T21:28:49Z
AUTHORS (12)
ABSTRACT
Purpose While surgical resection is a cornerstone of cancer treatment, local and distant recurrences continue to adversely affect outcome in significant proportion patients. Evidence that an alternative debulking strategy involving radiofrequency ablation (RFA) induces antitumor immunity prompted the current investigation efficacy performing RFA prior (pre-resectional RFA) preclinical mouse model. Experimental Design Therapeutic systemic immune responses were assessed following pre-resectional treatment murine CT26 colon adenocarcinoma. Results Treatment with significantly delayed tumor growth improved overall survival compared sham surgery, RFA, or alone. Mice group achieved complete response demonstrated durable upon re-challenge. Failure achieve therapeutic benefit immunodeficient mice confirmed control by depends on intact adaptive rather than changes physical parameters make ablated tumors more amenable excision. causes marked increase intratumoral CD8+ T lymphocyte infiltration, thus substantially enhancing ratio effector cells: FoxP3+ regulatory cells. Importantly, increases number antigen-specific cells within microenvironment tumor-draining lymph node but had no impact infiltration myeloid-derived suppressor cells, M1 macrophages M2 at sites peripheral lymphoid organs (i.e., spleen). Finally, primary through mechanism cell-mediated immunity. Conclusion Improved elicited support translational potential this neoadjuvant for patients high-risk recurrence.
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