Influence of radiofrequency thermal ablation on CD4+ T cell subsets in the patients with liver cancer
Creators: name: Kikodze, Nino
name: Iobadze, Manana
name: Pantsulaia, Ia
name: Nanava, Nino
name: Lemonjava, Maka
name: Chigvinidze, Nino
name: Malkhaz, Malkhaz
name: Janikashvili, Nona
name: Chikovani, Tinatin
Publisher: name: F1000Research
Year: 2016

description: The purpose of immunotherapy is to expose tumor under the influence of immune surveillance. The side effect of relatively new interstitial therapy – radiofrequency thermal ablation (RFA) is regarded as wide spectrum tumor antigen release followed by tumor-specific immune response.<br><br>     We aimed to investigate a short-term impact of RFA on the frequency of different phenotypes of CD4 T cells in the peripheral blood of primary and metastatic liver cancer patients. Our results demonstrate that the frequency of total circulating CD4 T lymphocytes was comparable between the patients and controls. CD4<sup>high+</sup> /CD4<sup>low+</sup> balance was slightly shifted toward CD4<sup>low+</sup>. The percentages of CD45RA, CD45RO, HLA-DR, CD39 cells were separately quantified within CD4<sup>low</sup> and CD4<sup>high</sup> populations. CD45RA(naïve) cells were significantly reduced in the cancer patients. This decrease was strongly associated with both – CD4<sup>low</sup> and CD4<sup>high</sup> populations of patients' T cells. Neither RFA treatment nor liver resection caused any changes of this parameter. CD45RO expression was largely overlapped with both CD4<sup>low</sup> and CD4<sup>high</sup> subsets, comprising activated and non-activated compartments of T cells. The frequency of CD4<sup>low</sup>CD45RO<sup>+ </sup>cells was decreased 1.5 times in patients compared to control. Whereas the percentage of CD4<sup>high+</sup>CD45RO cells was significantly elevated, that may indicate the presence of specific memory anti-tumor T cells in patients. HLA-DR marker expression was largely overlapped with activated CD4<sup>low </sup>compartment.There was 10-fold increase of CD4<sup>low+</sup>HLA-DRT cells (effector/activated) compared to control – result of ongoing anti-tumor immune response. RFA procedure and surgery did not significantly change the frequencies of CD4CD45RO and CD4HLA-DR T cells. The percentage of CD39cells was doubled within the patients’ CD4 T cells. This increase was strongly associated with both – CD4<sup>low</sup> and CD4<sup>high</sup> populations of patients' T cells. Of note, in both groups, patients and controls, CD39 expression was largely overlapped with CD4<sup>low</sup> subset, comprising the activated compartment of this population.RFA treatment favored to the significant reduction the percentage of CD39CD4 cells in the total CD4T cells, although no changes were observed in the group of patients with surgical resection.<br><br>     We suppose that one of the important effect of RFA on liver tumor relies on the destructive impact of RFA on CD4CD39 T cells responsible for generation of adenosine, which results in instant inhibition of immune response, recruitment of Treg cells to the tumor site and establishment of immunosuppressive environment. Herein, we describe that RFA exerted the immune modulatory effects on distinct subsets of circulating CD4<sup>+</sup> T cells in liver cancer patients. Further investigations are intended to clarify the long-term advantages of immunomodulatory RFA procedure, in comparison with the surgical intervention, in patients with  liver cancer.