Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group

Terheyden, Patrick; Kortüm, Anne-Katrin; Schulze, Hans‐Joachim; Durani, Benjamin; Remling, Roland; Mauch, Cornelia; Junghans, Volker; Schadendorf, Dirk; Beiteke, Ulrike; Jünger, Michael; Becker, Jürgen C.; Bröcker, Eva B.

doi:10.1007/s00432-006-0182-9

Cited by 33 publications

(22 citation statements)

References 26 publications

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“…We therefore propose that stimulation of TLR, IL-1R, IL-18R, and IL-12R may all favor the development of CHS to DNTB or other Ags, as reported for IL-12 (14). Consequently, NLR activation may be an interesting target as an adjuvant for vaccines and tumor vaccination, and it should be noted here that DNCB has been used to promote inflammation and favor immunerejection in metastatic melanoma patients (31).…”

Section: Discussionmentioning

confidence: 99%

Danger Signaling through the Inflammasome Acts as a Master Switch between Tolerance and Sensitization

Watanabe

Gehrke

Contassot

et al. 2008

The Journal of Immunology

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Efficient priming of adaptive immunity depends on danger signals provided by innate immune pathways. As an example, inflammasome-mediated activation of caspase-1 and IL-1β is crucial for the development of reactive T cells targeting sensitizers like dinitrofluorobenzene (DNFB). Surprisingly, DNFB and dinitrothiocyanobenzene provide cross-reactive Ags yet drive opposing, sensitizing vs tolerizing, T cell responses. In this study, we show that, in mice, inflammasome-signaling levels can be modulated to turn dinitrothiocyanobenzene into a sensitizer and DNFB into a tolerizer, and that it correlates with the IL-6 and IL-12 secretion levels, affecting Th1, Th17, and regulatory T cell development. Hence, our data provide the first evidence that the inflammasome can define the type of adaptive immune response elicited by an Ag, and hint at new strategies to modulate T cell responses in vivo.

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Section: Discussionmentioning

confidence: 99%

Danger Signaling through the Inflammasome Acts as a Master Switch between Tolerance and Sensitization

Watanabe

Gehrke

Contassot

et al. 2008

The Journal of Immunology

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“…This led to local therapeutic response rates in 37 % of patients. In a retrospective analysis of 72 patients treated with a combination of DNCB and DTIC IV, Terheyden et al [427] found response rates of 62 % in patients with stage III disease, yet only of 9 % in patients with stage IV disease. The latter finding was not superior to DTIC alone.…”

Section: Immunotherapymentioning

confidence: 99%

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Pflugfelder

Kochs

Blum

et al. 2013

J Deutsche Derma Gesell

181

148

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“…Terheyden et al (34) used dinitrochlorobenzene to induce contact dermatitis, which in combination with DTIC therapy, was used to treat metastatic MM. The objective response rate was 62% in patients with stage III MM (n=39) and 9% in those with stage IV MM (n=33), and >50% of patients remained progression-free for 1 year regardless of the stage of MM (35).…”

Section: Discussionmentioning

confidence: 99%

Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A clinical study

Chen

Zhao

et al. 2016

Oncology Letters

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Abstract. The present study aimed to evaluate the efficacy and safety of in situ immunotherapy with dinitrophenyl (DNP) hapten in combination with laser therapy for patients with malignant melanoma (MM). Between February 2008 and March 2012, 72 patients with stage III or IV MM were enrolled. Patients received in situ DNP alone (n=32) or in combination with laser therapy (n=32), and each group received dacarbazine chemotherapy. The levels of peripheral cluster of differentiation (CD)4 + CD25 + regulatory T cells (Tregs), interleukin (IL)-10 and tumor growth factor (TGF)-β were detected by ELISA. The association between delayed-type hypersensitivity (DTH) and survival time was evaluated. Although peripheral Treg levels significantly decreased over time in the two groups (P<0.001), there was no significant difference between the treatment groups (P= 0.098). Patients receiving the combination treatment exhibited significantly higher interferon-γ production by CD8 + and CD4 + T cells (both P<0.001), as well as significantly reduced levels of IL-10, TGF-β1 and TGF-β2. In addition, patients in the combination treatment group experienced significantly longer overall survival (OS; P=0.024) and disease-free survival (DFS; P=0.007) times; a DTH response of ≥15 mm was also associated with increased OS time and DFS time (P≤0.001). Finally, no severe adverse events were observed in either treatment group. Overall, in situ immunization with DNP in combination with laser immunotherapy may activate focal T cells, producing a regional antitumor immune response that increases cell-mediated immunity and improves survival in MM patients. Thus, this may represent a novel therapeutic strategy for patients with unresectable, advanced MM. IntroductionDerived from neural crest cells, malignant melanoma (MM) accounts for ~1.5% of all tumors and is the cutaneous malignancy with the highest mortality rate (1). There are >10 million new cases of MM diagnosed every year (1). In total, ~21% of MM patients present with focal skin metastasis and 50% with regional lymph node metastasis (1). MM patients with distant metastasis (stage IV) usually have poor prognoses, with a median survival time of 5-8 months, and the ≥5-year survival rate is <2% (2). With social and economic development, the incidence of MM is increasing each year (3).The poor prognosis of MM patients is reflective of the lack of an effective therapy. Systemic chemotherapy, including mono-and poly-chemotherapies, immunomodulatory therapies and vaccination therapy with dendritic cells (DCs) or genetically modified tumor cells, remains controversial (2). Although there is evidence showing that the combined use of interleukin (IL)-2, interferon (IFN) and chemotherapeutics may achieve a response rate as high as 64% (4,5), the efficacy of systemic therapy remains disappointing; systemic monotherapy usually achieves a clinical response rate of <15% (6-10). However, prospective, randomized clinical trials have shown no evidence that other drugs are superior to dacarbazine (DTIC) for MM pa...

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Chemoimmunotherapy for cutaneous melanoma with dacarbazine and epifocal contact sensitizers: results of a nationwide survey of the German Dermatologic Co-operative Oncology Group

Abstract: Epifocal DNCB combined with DTIC is effective in patients with regionally metastasized melanoma not amenable to surgery or isolated limb perfusion, whereas in stage IV disease in spite of few durable remissions the addition of DNCB does not improve the therapeutic efficacy of DTIC.

Cited by 33 publications

References 26 publications

Danger Signaling through the Inflammasome Acts as a Master Switch between Tolerance and Sensitization

Danger Signaling through the Inflammasome Acts as a Master Switch between Tolerance and Sensitization

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

Dinitrophenyl hapten with laser immunotherapy for advanced malignant melanoma: A clinical study

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