Universität zu Köln

Klein, Sebastian, Mauch, Cornelia, Wagener-Ryczek, Svenja, Schoemmel, Maximilian, Buettner, Reinhard, Quaas, Alexander and Helbig, Doris (2019). Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy. Cancer Immunol. Immunother., 68 (6). S. 973 - 983. NEW YORK: SPRINGER. ISSN 1432-0851

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Abstract

BackgroundPleomorphic dermal sarcomas (PDS) are sarcomas of the skin with local recurrences in up to 28% of cases, and distant metastases in up to 20%. Although recent evidence provides a strong rational to explore immunotherapeutics in solid tumors, nothing is known about the immune environment of PDS.MethodsIn the current study, a comprehensive immune-phenotyping of 14 PDS using RNA and protein expression analyses, as well as quantitative assessment of immune cells using an image-analysis tool was performed.ResultsThree out of 14 PDS revealed high levels of CD8-positive tumor-infiltrating T-lymphocytes (TILs), also showing elevated levels of immune-related cytokines such as IL1A, IL2, as well as markers that were very recently linked to enhanced response of immunotherapy in malignant melanoma, including CD27, and CD40L. Using a multivariate analysis, we found a number of differentially expressed genes in the CD8-high group including: CD74, LYZ and HLA-B, while the remaining cases revealed enhanced levels of immune-suppressive cytokines including CXCL14. The CD8-high PDS showed strong MHC-I expression and revealed infiltration by PD-L1-, PD-1- and LAG-3-expressing immune cells. Tumor-associated macrophages (TAMs) predominantly consisted of CD68+, CD163+, and CD204+M2 macrophages showing an accentuation at the tumor invasion front.ConclusionsTogether, we provide first explorative evidence about the immune-environment of PDS tumors that may guide future decisions whether individuals presenting with advanced PDS could qualify for immunotherapeutic options.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klein, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagener-Ryczek, Svenja UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoemmel, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Helbig, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-147136
DOI:	10.1007/s00262-019-02339-3
Journal or Publication Title:	Cancer Immunol. Immunother.
Volume:	68
Number:	6
Page Range:	S. 973 - 983
Date:	2019
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1432-0851
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ATYPICAL FIBROXANTHOMAS; ANTI-PD-L1 ANTIBODY; CTLA-4 BLOCKADE; SQUAMOUS-CELL; PD-1 BLOCKADE; OPEN-LABEL; CANCER; TUMOR; EXPRESSION; DIFFERENTIATION Multiple languages Oncology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/14713