Activation of dendritic cells by local ablation of hepatocellular carcinoma

Ali, M Y; Grimm, Christian; Ritter, M.; Mohr, Leonhard; Allgaier, Hans-Peter; Weth, Robert; Böcher, Wulf O.; Endrulat, Katja; Blum, Hubert E.; Geißler, Michael

doi:10.1016/j.jhep.2005.04.016

Cited by 116 publications

(82 citation statements)

References 17 publications

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“…Those studies demonstrated treatment-induced generation of a protective tumor-specific T cell response to tumor rechallenge. Recent reports of radio frequency thermal ablation in HCC patients complements our findings by showing that the activation of dendritic cells (39) and the expansion of tumor-specific ex vivo T cell responses (40) occur after treatment. Our study differs from these in that the target epitopes/Ags are defined and the development of responses is associated with an improved clinical outcome.…”

Section: Discussionsupporting

confidence: 82%

Unmasking of α-Fetoprotein-Specific CD4+ T Cell Responses in Hepatocellular Carcinoma Patients Undergoing Embolization

Ayaru

Pereira

Alisa

et al. 2007

The Journal of Immunology

156

107

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Necrosis of tumor cells can activate both innate and adaptive antitumor immunity. However, there is little information on the effects of necrosis-inducing cancer treatments on tumor-specific T cell immune responses in humans. We studied the effects of a necrosis-inducing treatment (embolization) on anti-α-fetoprotein (AFP)-specific CD4+ T cell responses in hepatocellular carcinoma (HCC) patients and controls using an array of AFP-derived peptides. In this study, we show that AFP-specific CD4+ T cell responses to three immunodominant epitopes in HCC patients were significantly expanded during (p < 0.0001) and after embolization (p < 0.002). The development of higher frequencies of AFP-specific CD4+ T cells after treatment were significantly associated with the induction of >50% necrosis of tumor and an improved clinical outcome (p < 0.007). In addition, we identified two novel HLA-DR-restricted AFP-derived CD4+ T cell epitopes (AFP137–145 and AFP249–258) and showed that the CD4+ T cells recognizing these epitopes produce Th1 (IFN-γ and TNF-α) but not Th2 (IL-5)-type cytokines. AFP137–145-, AFP249–258-, and AFP364–373-specific CD4+ T cells were detected in HCC patients but not in patients with chronic liver diseases or healthy donors. In conclusion; our study shows that induction of tumor necrosis by a conventional cancer treatment can unmask tumor rejection Ag cell-mediated immunity and provides a rationale for combining embolization with immunotherapy in HCC patients.

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Section: Discussionsupporting

confidence: 82%

Unmasking of α-Fetoprotein-Specific CD4+ T Cell Responses in Hepatocellular Carcinoma Patients Undergoing Embolization

Ayaru

Pereira

Alisa

et al. 2007

The Journal of Immunology

156

107

View full text Add to dashboard Cite

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“…RFA of HCC induces specific T-cell responses against liver tumors in human and rabbit (8,11). Moreover, activated dendritic cells were detected in peripheral blood of HCC patients after RFA (9). These previous reports indicate that RFA treatment can induce antitumor immune responses against HCC (8)(9)(10)(11).…”

Section: Discussionmentioning

confidence: 64%

“…RFA of HCC can generate HCC-specific T cells in peripheral blood (8). Activation of dendritic cells in human peripheral blood is also observed after this treatment (9). Thus, RFA can induce immunogenic tumor cell death and subsequently tumor-specific immune responses (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

“…Activation of dendritic cells in human peripheral blood is also observed after this treatment (9). Thus, RFA can induce immunogenic tumor cell death and subsequently tumor-specific immune responses (8)(9)(10)(11). However, multicentric development of HCC in the cirrhotic liver frequently results in tumor recurrence even after the apparent curative treatment of HCC by RFA (12).…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Effect after Radiofrequency Ablation of Murine Hepatoma Is Augmented by an Active Variant of CC Chemokine Ligand 3/Macrophage Inflammatory Protein-1α

et al. 2010

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Several chemokines are used for immunotherapy against cancers because they can attract immune cells such as dendritic and cytotoxic T cells to augment immune responses. Radiofrequency ablation (RFA) is used to locally eliminate cancers such as hepatocellular carcinoma (HCC), renal cell carcinoma, and lung cancer. Because HCC often recurs even after an eradicative treatment with RFA, additional immunotherapy is necessary. We treated tumor-bearing mice by administering ECI301, an active variant of CC chemokine ligand 3, after RFA. Mice were injected s.c. with BNL 1ME A.7R.1, a murine hepatoma cell line, in the bilateral flank. After the tumor became palpable, RFA was done on the tumor of one flank with or without ECI301. RFA alone eliminated the treated ipsilateral tumors and retarded the growth of contralateral non-RFA-treated tumors accompanied by massive T-cell infiltration. Injection of ECI301 augmented RFA-induced antitumor effect against non-RFA-treated tumors when administered to wild-type or CCR5-deficient but not CCR1-deficient mice. ECI301 also increased CCR1-expressing CD11c + cells in peripheral blood and RFA-treated tumors after

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“…Unlike surgical resection, tumor ablation treatment generates tumor cell necrosis (11), followed by the release of tumor-associated antigens (12). These antigens can be uptaken, processed, and presented by dendritic cells (10, 13), and then an antigen-specific T-cellmediated immune response can be induced (9). If this induction is sufficiently steady and reliable, it may provide the basis for adjuvant immunotherapy, which is an attractive strategy.…”

Section: Radiofrequency Ablation For Hepatocellular Carcinoma Inducesmentioning

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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Activation of dendritic cells by local ablation of hepatocellular carcinoma

Cited by 116 publications

References 17 publications

Unmasking of α-Fetoprotein-Specific CD4+ T Cell Responses in Hepatocellular Carcinoma Patients Undergoing Embolization

Unmasking of α-Fetoprotein-Specific CD4+ T Cell Responses in Hepatocellular Carcinoma Patients Undergoing Embolization

Antitumor Effect after Radiofrequency Ablation of Murine Hepatoma Is Augmented by an Active Variant of CC Chemokine Ligand 3/Macrophage Inflammatory Protein-1α

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

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