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Abstract:

Objectives: Cidofovir (CDV) is known to have antiproliferative effects on HPV+ transformed cells. Clinical evidence showed that local treatment of HPV lesions with CDV reduced the growth of untreated lesions at a distant site. Here, the underlying mechanism for this distant effect was investigated. Methods: nu/nu NMRI mice were subcutaneously injected with SiHa cells (tumor 1, T1). When animals developed visible tumors, they were subdivided into 3 groups: CDV-treated; PBS-treated and untreated. Intratumoral treatment of T1 was done for 3 weeks and then a second tumor (T2) was induced, which was not treated. Two mice of each group were sacrificed weekly to evaluate immune cells in tumors by flow cytometry. Weight and tumor size were measured weekly. Results: T2 grew faster and bigger in the PBS-treated and untreated groups than in the CDV-treated group. Because of its small size in the CDV-treated group, T2 could only be evaluated by flow cytometry after 3 weeks of tumor induction. Neutrophils were the most abundant immune cells in the tumors and decreased in T1 after 6 weeks of onset of CDV treatment. The amount of macrophages and γδ T-cells in both T1 and T2 were elevated in the CDV-treated group, compared to the other groups. A decreased amount of tumor associated macrophages was found in T2 6 weeks after onset of CDV treatment compared to untreated or PBS treated groups. Conclusion: These preliminary data suggest that intratumoral CDV had an indirect effect on the immune response of mice, diminishing the size of T2.