Systemic inflammatory response and downmodulation of peripheral CD25 super(+)Foxp3 super(+) T-regulatory cells in patients undergoing radiofrequency thermal ablation for lung cancer

Radiofrequency thermal ablation (RFTA) is a local tumor-destructing technique that can potentially modulate the host immune response through mechanisms that are not clearly defined. We assessed whether RFTA could affect multiple systemic inflammatory and immunological parameters, including CD25 super(+)Foxp3 super(+) cells, in patients with primary or metastatic lung tumors. Three days after RFTA, a moderate and temporary systemic inflammatory response developed, as demonstrated by the increase in peripheral neutrophils and monocytes and in plasma levels of proinflammatory chemokines (MIP-1 alpha , MIP-1 beta , eotaxin, and interleukin[IL]-8) and acute phase reactants (complement C3 and C4, serum amyloid, alpha 1 antichymotrypsin, and C-reactive protein). Moreover, we found a concomitant release of the anti-inflammatory factor IL-10. Thirty days after RFTA, a significant reduction in CD25 super(+)Foxp3 super(+) counts with an increase in CD4 super(+) T-cell proliferation and number of interferon- gamma -secreting cells was observed. The reduction in CD25 super(+)Foxp3 super(+) cells lasted up to 90 days after treatment. The use of RFTA in lung cancer patients has an immunomodulatory activity: it induces a self-limiting systemic inflammation early and later a reduction of circulating CD25 super(+)Foxp3 super(+) Tregs. In addition to tumor ablation, downmodulation of this regulatory subset might be an important mechanism involved in the long-term clinical efficacy of RFTA.