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

  • Sebastian Klein
  • Cornelia Mauch
  • Svenja Wagener-Ryczek
  • Maximilian Schoemmel
  • Reinhard Buettner
  • Alexander Quaas
  • Doris HelbigEmail author
Original Article

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.

Keywords

Immune-phenotyping Major histocompatibility complex (MHC) NanoString Pleomorphic dermal sarcoma (PDS) RNA analysis Tumor-infiltrating lymphocytes (TILs) 

Abbreviations

CPI

Immune checkpoint inhibitors

FFPE

Formalin-fixated and paraffin-embedded

M1

Type 1 macrophages

M2

Type 2 macrophages

PDCD1

Programmed cell death 1

PDS

Pleomorphic dermal sarcoma

TAM

Tumor-associated macrophages

TIGIT

T cell immunoreceptor with Ig and ITIM domains

TMA

Tissue microarray

Notes

Acknowledgements

We thank Wiebke Jeske and Susann Zupp for technical assistance performing the TMA, mRNA in-situ and immunohistochemical staining.

Author contributions

Sebastian Klein, Alexander Quaas and Doris Helbig designed the study, selected cases, conceived and carried out all experiments, analyzed and interpreted results, generated figures and tables, and performed literature research, and writing of the manuscript. Svenja Wagener-Ryczek and Maximilian Schoemmel were involved in performing the NanoString analyses. Cornelia Mauch and Reinhard Buettner were involved in designing the project. All the authors were involved in writing the paper and approved the final version of the manuscript.

Funding

This work was supported by the Deutsche Forschungsgemeinschaft through the SFB829 (Z4 to Doris Helbig and Cornelia Mauch) and the Else Kröner-Fresenius Stiftung (EKFS-2014-A06 and 2016_Kolleg.19 to Sebastian Klein).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki as reflected by the approval of the institution’s human research review committee (Ethics Committee of the Medical Faculty of University of Cologne: registration no. 15–307).

Informed consent

All patients gave written informed consent to the use of their tumors and their data for research.

Animal source

Not applicable.

Cell line authentication

Not applicable.

Supplementary material

262_2019_2339_MOESM1_ESM.pdf (105 kb)
Supplementary file1 (PDF 105 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Else Kröner Forschungskolleg Clonal Evolution in CancerUniversity Hospital CologneCologneGermany
  2. 2.Department of DermatologyUniversity Hospital CologneCologneGermany
  3. 3.Institute of PathologyUniversity Hospital CologneCologneGermany

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