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Erschienen in: Cancer Immunology, Immunotherapy 6/2019

08.04.2019 | Original Article

Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy

verfasst von: Sebastian Klein, Cornelia Mauch, Svenja Wagener-Ryczek, Maximilian Schoemmel, Reinhard Buettner, Alexander Quaas, Doris Helbig

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2019

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Abstract

Background

Pleomorphic 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.

Methods

In 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.

Results

Three 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.

Conclusions

Together, 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.
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Literatur
7.
Zurück zum Zitat Borradori L, Sutton B, Shayesteh P, Daniels GA (2016) Rescue therapy with anti-programmed cell death protein 1 inhibitors (PD-1) of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in 5 cases. Br J Dermatol 175(6):1382-1386 https://doi.org/10.1111/bjd.14642 CrossRefPubMed Borradori L, Sutton B, Shayesteh P, Daniels GA (2016) Rescue therapy with anti-programmed cell death protein 1 inhibitors (PD-1) of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in 5 cases. Br J Dermatol 175(6):1382-1386 https://​doi.​org/​10.​1111/​bjd.​14642 CrossRefPubMed
12.
Zurück zum Zitat Barberis I, Martini M, Iavarone F, Orsi A (2016) Available influenza vaccines: immunization strategies, history and new tools for fighting the disease. J Prev Med Hyg 57:E41–E46PubMedPubMedCentral Barberis I, Martini M, Iavarone F, Orsi A (2016) Available influenza vaccines: immunization strategies, history and new tools for fighting the disease. J Prev Med Hyg 57:E41–E46PubMedPubMedCentral
22.
Zurück zum Zitat Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168PubMed
Metadaten
Titel
Immune-phenotyping of pleomorphic dermal sarcomas suggests this entity as a potential candidate for immunotherapy
verfasst von
Sebastian Klein
Cornelia Mauch
Svenja Wagener-Ryczek
Maximilian Schoemmel
Reinhard Buettner
Alexander Quaas
Doris Helbig
Publikationsdatum
08.04.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 6/2019
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-019-02339-3

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