Use of interferon-alpha in two patients with Merkel cell carcinoma positive for Merkel cell polyomavirus

Biver-Dalle, C.; Nguyen, Thierry; Touzé, Antoine; Saccomani, Clarisse; Penz, S.; Cunat-Peultier, Sandrine; Riou-Gotta, Marie-Odile; Humbert, Philippe; Coursaget, Pierre; Aubin, F.

doi:10.3109/0284186x.2010.512924

Cited by 34 publications

(20 citation statements)

References 9 publications

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“…the source which most of the immuno-dominant T cell epitopes are derived from 11 . In line with this, treatment of two MCC patients with MCPyV positive primary tumors and metastasis with interferon alpha had no therapeutic effect 47 .…”

Section: Discussionmentioning

confidence: 85%

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Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

Ritter

Fan

Paschen

et al. 2017

Sci Rep

113

103

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Merkel cell carcinoma (MCC) is a rare and aggressive, yet highly immunogenic skin cancer. The latter is due to its viral or UV-associated carcinogenesis. For tumor progression MCC has to escape the host’s immuno-surveillance, e.g. by loss of HLA class-I expression. Indeed, a reduced HLA class-I expression was observed in MCC tumor tissues and MCC cell lines. This reduced HLA class-I surface expression is caused by an impaired expression of key components of the antigen processing machinery (APM), including LMP2 and LMP7 as well as TAP1 and TAP2. Notably, experimental provisions of HLA class-I binding peptides restored HLA class-I surface expression on MCC cells. Silencing of the HLA class-I APM is due to histone deacetylation as inhibition of histone deacetylases (HDACs) not only induced acetylation of histones in the respective promoter regions but also re-expression of APM components. Thus, HDAC inhibition restored HLA class-I surface expression in vitro and in a mouse xenotransplantation model. In contrast to re-induction of HLA class-I by interferons, HDAC inhibitors did not interfere with the expression of immuno-dominant viral proteins. In summary, restoration of HLA class-I expression on MCC cells by epigenetic priming is an attractive approach to enhance therapies boosting adaptive immune responses.

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Section: Discussionmentioning

confidence: 85%

“…Immunohistochemistry (IHC) was performed on FFPE tissue as describe before 47 . In short antigens were retrieved using a citrate buffer (Retrieval solution, cat.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

Ritter

Fan

Paschen

et al. 2017

Sci Rep

113

103

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“…Immunologic treatment of mcc using interferons and the toll-like receptor 7 agonist imiquimod has been tried, with mixed response [8][9][10][11][12][13][14] . Epidemiologic and experimental evidence both strongly suggest that mcc is controlled by the immune system [18][19][20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

“…After interdisciplinary tumour board presentation, off-label intralesional treatment with 1-2×10 6 IU interferon alfa-2a once weekly, accompanied by topical imiquimod 5% cream 3 times weekly, was initiated because of favourable case reports in the literature [8][9][10][11][12][13][14] .…”

Section: Case Descriptionmentioning

confidence: 99%

“…High remission rates are reported after chemotherapy; however, no improvement in overall survival has been achieved 6,7 . Several experimental treatments with immunomodulatory drugs and with molecularly-targeted agents have been tried with moderate success [8][9][10][11][12][13][14] . Here, we report the case of an elderly woman with regionally metastasized mcc that responded to a combination of local skin-directed, intralesional, and systemic immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Immunotherapy with Imiquimod and Interferon Alfa for Metastasized Merkel Cell Carcinoma

et al. 2016

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Merkel cell carcinoma (mcc) is a highly aggressive neuroendocrine tumour of the skin. Remission rates are high with chemotherapy in patients with metastasis, but without any improvement in overall survival.We present the case of a 90-year-old woman with facial mcc. After radiation and surgery, the mcc recurred with widespread cutaneous and regional lymph node metastases. The metastases were treated with weekly intralesional injections of 1-2×10 6 IU interferon alfa-2a, accompanied by topical imiquimod 5% cream 3 times weekly. After partial regression, subcutaneous pegylated interferon alfa-2b was added at a dose of 30 μg weekly, which was then increased to 50 μg weekly. At 4 months after the start of immunotherapy, all cutaneous metastases and the intralesionally treated lymph node metastases receded. Interruption or reduction of systemic interferon application resulted in locoregional relapses that were successfully treated with surgery or intralesional interferon injections. The patient remains alive 30 months after initiation of immunotherapy, suggesting that locally metastasized mcc might be able to be controlled with local and systemic immunotherapy.

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Merkel cell carcinoma: Do you know your guidelines?

Miles

Goldenberg

2015

Head & Neck

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Use of interferon-alpha in two patients with Merkel cell carcinoma positive for Merkel cell polyomavirus

Cited by 34 publications

References 9 publications

Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

Epigenetic priming restores the HLA class-I antigen processing machinery expression in Merkel cell carcinoma

Immunotherapy with Imiquimod and Interferon Alfa for Metastasized Merkel Cell Carcinoma

Merkel cell carcinoma: Do you know your guidelines?

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