Radiofrequency Thermal Ablation for Hepatocellular Carcinoma Stimulates Autologous NK-Cell Response

Zerbini, Alessandro; Pilli, Massimo; Laccabue, Diletta; Pelosi, Giorgio; Molinari, Atim; Negri, Elisa; Cerioni, S.; Fagnoni, Francesco; Soliani, P.; Ferrari, Carlo; Missale, Gabriele

doi:10.1053/j.gastro.2009.12.051

Cited by 164 publications

(117 citation statements)

References 37 publications

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“…Interestingly, recent studies also showed a role for some currently available therapeutic approaches in boosting the natural immune response against HCC. For example, it could be shown that RFTA increases the costimulatory capacity of antigen-presenting cells (APCs) and boosts NK cell activity [75,76]. This is probably mediated by the release of tumor material by necrosis and thus in a proinflammatory context.…”

Section: Perspectives For Treatmentmentioning

confidence: 99%

Immunobiology of hepatocellular carcinoma

Flecken

Spangenberg

Thimme

2011

Langenbecks Arch Surg

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Hepatocellular carcinoma (HCC) is a tumor of increasing incidence and high mortality worldwide. Diagnosis of HCC is often difficult, especially at early stages of disease. Additionally, current treatment options are limited. HCC usually develops in an environment of chronic liver disease. The immune system has an important role in shaping this environment, especially in chronic viral hepatitis, the leading cause of HCC. However, the immune system also plays a role in natural immunity against HCC although this is apparently not sufficient to control the majority of tumors. This failure in tumor control is due to multiple immunomodulatory mechanisms employed by HCC to subvert the immune system. In this review, we will summarize the current knowledge about the role of the immune system in hepatocarcinogenesis. Additionally, we will describe the mechanisms used by the immune system to control established lesions and the reasons why these immune responses apparently fail so often. Finally, possible implications for the design of novel immunotherapeutic strategies will be discussed.

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Section: Perspectives For Treatmentmentioning

confidence: 99%

Immunobiology of hepatocellular carcinoma

Flecken

Spangenberg

Thimme

2011

Langenbecks Arch Surg

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“…However, long-term prognosis of HCC is not satisfactory, primarily because intrahepatic recurrence is extremely frequent. Reported risk factors for recurrence include tumor-related factors, such as the number and size of nodules, liver factors, and virus factors, including immune responses by the host [13][14][15]. Since HBV viral load can be attenuated with potential anti-viral agents, such as entecavir, it is clinically important to evaluate the effects of viral load on recurrence.…”

Section: Introductionmentioning

confidence: 99%

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

et al. 2011

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“…In view of the highly complex nature of the human immune system, patient prognoses might not be determined only by the CTL response. Previous studies have demonstrated that the release of tumor-derived antigens by necrosis-inducing treatment causes sufficient signaling to activate not only antigen-specific CTL response but also antigen-specific helper T-cell response (35,36), antigen-specific antibody response (36), and nonantigen-specific natural killer cell response (37). However, the mechanisms for cancer escape from immunosurveillance would suppress the efficiency of these immune responses (38).…”

Section: Discussionmentioning

confidence: 99%

Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

et al. 2011

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Abstract. Glypican-3 (GPC3), a carcinoembryonic antigen, is an ideal target for anticancer immunotherapy against hepatocellular carcinoma (HCC). In this study, we attempted to compare the induction of the GPC3-specific T-cell-mediated immune response after locoregional therapies in HCC patients and tumor-bearing mice. Twenty-seven HCC patients treated with locoregional therapies, including radiofrequency ablation (RFA), surgical resection and transcatheter arterial chemoembolization (TACE), were prospectively enrolled in this study. Additionally, we performed RFA experiments using a mouse model. GPC3-specific T-cell response was investigated pretreatment and post-treatment by an interferon-γ enzyme-linked immunospot assay using peripheral blood mononuclear cells from HCC patients and lymph node cells from tumor-bearing mice. Circulating GPC3-specific cytotoxic T lymphocytes (CTLs) were increased in 5 of 9 patients after RFA and in 4 of 9 patients after TACE, but in only 1 of 9 patients after surgical resection. All 7 patients with GPC3-expressing HCCs exhibited an increase in GPC3-specific CTLs after RFA or TACE, whereas none of the 7 patients did after surgical resection. The number of increased GPC3-specific CTLs after RFA was significantly larger than that after surgical resection (P= 0.023). Similarly, the frequency of GPC3-specific CTLs after RFA was significantly greater than that after surgical resection in the mouse model (P=0.049). We validated for the first time the stronger effect on the immune system brought by RFA compared with surgical resection for HCC patients and tumor-bearing mice. Combined treatment of RFA and immunotherapy is a reasonable strategy against HCC. IntroductionHepatocellular carcinoma (HCC) is one of the most common and most serious cancers worldwide (1). Locoregional therapies, including radiofrequency ablation (RFA), surgical resection, and transcatheter arterial chemoembolization (TACE), are recognized as the gold-standard therapies for HCC patients whose cancer lesions are limited to the liver (2). However, the recurrence rate remains quite high despite potentially curative treatment (3,4). The reasons for this are as follows: first, a multicentric new tumor frequently occurs from underlying active hepatitis or cirrhosis and, second, a small tumor undetectable by imaging modalities frequently exists before treatment and would be left untreated (5). Therefore, the establishment of effective adjuvant therapy to prevent recurrence is urgently required, and Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

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Radiofrequency Thermal Ablation for Hepatocellular Carcinoma Stimulates Autologous NK-Cell Response

Cited by 164 publications

References 37 publications

Immunobiology of hepatocellular carcinoma

Immunobiology of hepatocellular carcinoma

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

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