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Introduction:The complexity of aggressive cancers implies that they may only be eradicated by adaptable systems (such as the immune system). Immuno-modulators have efficacy in immunogenic malignancies but less benefit in prostate cancer. Here we study whether various local therapies may augment the immune response to distant tumors in a prostate cancer model.
Materials & Methods:Immuno-competent FVB mice were injected bilaterally with MycCaP cells to establish sub-cutaneous grafts. After establishment, the larger graft was treated by cryoablation, cautery, radiation (10 Gy) or en bloc excision. Mice were followed for 36 days, tumors were measured every 2 to 3 days, mice were sacrificed when tumors reached 2000mm3 or had tumor ulceration. In a second experiment an identical procedure was followed with mice sacrificed at 2 and 4 weeks and harvested for flow cytometry and IHC.
Results:All ablative therapies increased survival compared to control (p<0.05). Treatment of tumors by cryotherapy or cautery resulted in the longest median survival (34 days vs 25 for excision or radiation vs 12 days in control) and greatest delay in onset of exponential growth in the untreated distant tumor. All therapies increased CD3 positive cells in distant tumors. Cryotherapy and cauterization of a tumor increased the amount of IL-2 positive CD4 cells and IFNgamma positive CD8 cells in the distant tumor.
Conclusions:Local therapies, and particularly cryoablation and cauterization demonstrate potential systemic effects on anti-tumor immunity and may act as putative adjuncts to immuno-therapies for prostate cancer.