TY  - JOUR
A1  - Wendlinger, Simone
A1  - Wohlfarth, Jonas
A1  - Kreft, Sophia
A1  - Siedel, Claudia
A1  - Kilian, Teresa
A1  - Dischinger, Ulrich
A1  - Heppt, Markus V.
A1  - Wistuba-Hamprecht, Kilian
A1  - Meier, Friedegund
A1  - Goebeler, Matthias
A1  - Schadendorf, Dirk
A1  - Gesierich, Anja
A1  - Kosnopfel, Corinna
A1  - Schilling, Bastian
T1  - Blood eosinophils are associated with efficacy of targeted therapy in patients with advanced melanoma
JF  - Cancers
N2  - Background: Eosinophils appear to contribute to the efficacy of immunotherapy and their frequency was suggested as a predictive biomarker. Whether this observation could be transferred to patients treated with targeted therapy remains unknown. Methods: Blood and serum samples of healthy controls and 216 patients with advanced melanoma were prospectively and retrospectively collected. Freshly isolated eosinophils were phenotypically characterized by flow cytometry and co-cultured in vitro with melanoma cells to assess cytotoxicity. Soluble serum markers and peripheral blood counts were used for correlative studies. Results: Eosinophil-mediated cytotoxicity towards melanoma cells, as well as phenotypic characteristics, were similar when comparing healthy donors and patients. However, high relative pre-treatment eosinophil counts were significantly associated with response to MAPKi (p = 0.013). Eosinophil-mediated cytotoxicity towards melanoma cells is dose-dependent and requires proximity of eosinophils and their target in vitro. Treatment with targeted therapy in the presence of eosinophils results in an additive tumoricidal effect. Additionally, melanoma cells affected eosinophil phenotype upon co-culture. Conclusion: High pre-treatment eosinophil counts in advanced melanoma patients were associated with a significantly improved response to MAPKi. Functionally, eosinophils show potent cytotoxicity towards melanoma cells, which can be reinforced by MAPKi. Further studies are needed to unravel the molecular mechanisms of our observations.
KW  - melanoma
KW  - eosinophils
KW  - biomarker
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275137
SN  - 2072-6694
VL  - 14
IS  - 9
ER  - 
TY  - JOUR
A1  - Wobser, Marion
A1  - Siedel, Claudia
A1  - Kneitz, Hermann
A1  - Bröcker, Eva-Bettina
A1  - Goebeler, Mathias
A1  - Houben, Roland
A1  - Geissinger, Eva
T1  - Microvessel Density and Expression of Vascular Endothelial Growth Factor and its Receptors in Different Subtypes of Primary Cutaneous B-cell Lymphoma
JF  - Acta Dermato-Venereologica
N2  - A proangiogenic micromilieu is associated with a worse prognosis in systemic lymphoma. Hence, targeting the tumour microenvironment and its vasculature has evolved as a promising novel treatment strategy. The role of tumour neoangiogenesis in cutaneous B-cell lymphoma, however, has not yet been elucidated. Therefore, we examined the expression of vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 and VEGFR-2, as well as microvessel density by immunohistochemistry in paraffin-embedded specimens of different subtypes of primary cutaneous B-cell lymphomas, systemic diffuse large B-cell lymphoma, and cutaneous B-cell pseudolymphoma. Primary cutaneous large B-cell lymphoma (PCLBCL) were characterized by significantly higher intratumoral expression levels of VEGF and its receptors in comparison with the indolent lymphoma subtypes. Moreover, PCLBCL exhibited significantly higher intratumoral microvessel counts. Our study provides evidence that the most aggressive subtype of cutaneous B-cell lymphoma, PCLBCL, is characterized by a proangiogenic micromilieu.
KW  - microvessel density
KW  - vascular endothelial growth
KW  - B-cell lymphoma
KW  - subtypes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128608
VL  - 93
IS  - 6
ER  -