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Figure 2: Cytolytic activity of T cells measured by adenylate kinase (AK)
+
Figure 1: Stimulation index of CD8 T cells was determined by the ratio of release assay. AK release was quantifi ed by luminescence and expressed as
−
+
+
+
IFNγ CD8 vs. IFNγ CD8 T cells after stimulation with autologous tumor antigens. RLU. A signifi cant difference between patients with recurrence of malignancy
Shown are mean ± SD. IFNγ: interferon gamma; CRC: colorectal cancer; and patients with disease-free survival is shown after 12 months (P < 0.05)
HCC: hepatocellular carcinoma; RFA: radiofrequency ablation
only. Shown are mean ± SD. RFA: radiofrequency ablation; RLU: relative
luminescence units
Table 1: Summary of general data with entity of cirrhosis
and entity of primary in case of metastases
treatment. As these tissue samples were obtained by
Patient Entity Stage of disease 12 months after RFA
fine-needle biopsy prior to RFA, we decided to concentrate
Primary
on the measurement of CD8 cells. These cells are reported
+
CRC1 Colon descending Disease free
CRC2 Rectum Metastases to lung to be the most promising cell population for anti-tumor
CRC3 Rectum Disease free therapies. All patients still had significantly increased levels of
+
Cirrhosis CD8 cells containing cytotoxic T cells, NK cell and NK T cells
HCC1 Alcohol Disease free as well. Whether these observed cells are resting T cells or
HCC2 Alcohol Local recurrence any other activated form of T cell remains unclear.
CRC: colorectal cancer; HCC: hepatocellular carcinoma; RFA: radiofrequency
ablation
We observed no differences between patients with recurrence
therapies have shown encouraging survival rates similar to of malignancy or with disease-free survival. Interestingly,
R0 resection of tumors. [1,2,11] In addition, T cell vaccination cytolytic activity was significantly lower in the two patients
or vaccination with dendritic cells is regarded as a promising with tumor recurrence compared. Perhaps, recurrence of
strategy for the treatment of various tumor types such as malignancy is caused by an ineffective cytolytic/cytotoxic
+
malignant melanomas, [12-20] and high expectations have been activity of CD8 cells but needs to be confirmed with further
placed on cytokine-modulated immunotherapy for liver tumors. investigations.
It is well-known that RFA can induce an unspecific Prior data showed an enhanced tumor growth if RFA or
immune stimulation. Thus, thermal coagulation causes an resection of liver metastases of CRC were not properly
inflammatory reaction with lymph-plasma-cellular infiltration performed with remaining micrometastases due to hypoxia
that can be visualized as a hypervascular rim in contrast and growth factors induced by the process of wound
CT and contrast-enhanced ultrasound. This hypervascular healing. [21,22] This might indicate that the immune response
rim can be so intense as to impede proper assessment is not strong enough to control tumor growth or that the
[5]
of treatment success. We recently demonstrated a immune response is not tumor specific or not effective by
specific T cell response, after RFA application, toward the the lack of tumor-specific cytolytic cells.
[6]
orthotopic VX 2-tumor implantation in rabbit livers. In
the clinical setting, it was also shown that a tumor-specific Furthermore, the potential role of a tumor-specific immune
immune response could be detected in patients after RFA. response as a target for supportive adjuvant therapy after
Our preliminary study showed a significant appearance of RFA or resection of metastases has not yet been addressed.
tumor-specific CD4 and CD8 T cells in peripheral blood up Therefore, larger groups with a follow-up for more than
+
+
to 8 weeks after RFA. The cytolytic activity of isolated PBMC 6-12 months are needed to clarify whether lower cytolytic
was also significantly elevated. [8] activity levels are correlated with recurrence of malignancy
after local ablative therapies. This would suggest the need for
In this study, we investigated the presence of tumor-specific an effective combination of drugs with RFA to achieve a long
T cells and the cytolytic activity 12 months after RFA lasting strong cytolytic activity of the Th2 immune response.

Hepatoma Research | Volume 1 | Issue 2 | July 15, 2015 95