Elevated Heat Shock Protein 70 (HSP70) Serum Levels After Tumor Radiofrequency Ablation Might Represent a Favorable Prognostic Marker.

Radiofrequency (RF) ablation is a safe and effective method to locally treat malignancies of the liver, kidney and more recently lung. For the treatment of small tumors, long term results are comparable with outcome after surgical resection and better than current chemotherapies. RF-ablation has now been reported to induce heat shock protein (HSP) expression on sublethally damaged hepatocytes. HSPs are potent alarm signals for the immune system causing i.e. activation of T cells and dendritic cells. In addition to triggering immune responses directed against HSPs themselves, HSPs can carry antigens derived from those cells of which HSPs originated and thereby elicit specific immune reactions against these cellular epitopes.

We here analyzed serum samples of 22 patients to evaluate the systemic release of HSP70 using a specific HSP70 ELISA. Patients were followed for a median of 30 months until death or three years after the last RF-treatment. As a control group, sera from 20 patients undergoing diagnostic liver biopsy were screened.

The median increase of HSP70 in serum comparing levels before and one day after the procedures was 1.6-fold in the RF-ablation group, while no soluble HSP-70 could be detected in the control group before and after the biopsy. Nine patients showed a higher than two-fold increase of HSP70 in the serum after ten sessions of RF-ablation compared to levels prior to treatment. No correlation of HSP70 levels with tumor volume, the ablated non-malignant tissue or the total size of the necrosis was observed. In the subgroup of patients with elevated HSP-70 serum levels, 67% (6 out of 9) were alive at the end of follow up with only one suffering from progressive disease. In contrast, 61% (8 out of 13) of the other patients suffered from progressive disease or had deceased at the end of follow-up.

RF-ablation not only induces cellular HSP expression but also can lead to a systemic release of serum HSP70. Patients with strong increases in HSP-70 serum levels tended to have a better survival than patients without induction of HSP-70 in the serum. Thus, immunomodulation might represent an additional beneficial effect of RF-ablation besides local tumor destruction, since HSPs are strong stimuli for the immune system and can mediate tumor-specific T cell immunity.

No relevant conflicts of interest to declare.