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Desmoid tumors display a strong immune infiltration at the tumor margins and no PD-L1-driven immune suppression

  • Vasiliki SiozopoulouEmail author
  • Elly Marcq
  • Julie Jacobs
  • Karen Zwaenepoel
  • Christophe Hermans
  • Jantine Brauns
  • Siegrid Pauwels
  • Clément Huysentruyt
  • Martin Lammens
  • Johan Somville
  • Evelien Smits
  • Patrick Pauwels
Original Article

Abstract

Desmoid tumors (DTs) are local aggressive neoplasms, whose therapeutic approach has remained so far unsolved and in many instances controversial. Nowadays, immunotherapy appears to play a leading role in the treatment of various tumor types. Characterization of the tumor immune microenvironment (TME) and immune checkpoints can possibly help identify new immunotherapeutic targets for DTs. We performed immunohistochemistry (IHC) on 33 formalin-fixed paraffin-embedded (FFPE) tissue sections from DT samples to characterize the TME and the immune checkpoint expression profile. We stained for CD3, CD4, CD8, CD20, FoxP3, CD45RO, CD56, CD68, NKp46, granzyme B, CD27, CD70, PD1 and PD-L1. We investigated the expression of the markers in the tumoral stroma, as well as at the periphery of the tumor. We found that most of the tumors showed organization of lymphocytes into lymphoid aggregates at the periphery of the tumor, strongly resembling tertiary lymphoid organs (TLOs). The tumor expressed a significant number of memory T cells, both at the periphery and in the tumoral stroma. In the lymphoid aggregates, we also recognized a significant proportion of regulatory T cells. The immune checkpoint ligand PD-L1 was negative on the tumor cells in almost all samples. On the other hand, PD1 was partially expressed in lymphocytes at the periphery of the tumor. To conclude, we are the first to show that DTs display a strong immune infiltration at the tumor margins, with formation of lymphoid aggregates. Moreover, we demonstrated that there is no PD-L1-driven immune suppression present in the tumor cells.

Keywords

Desmoid tumors PD-L1 Immunotherapy Immunohistochemistry 

Abbreviations

CTLA-4

Cytotoxic T lymphocyte antigen-4

DT

Desmoid tumors

FAP

Familial adenomatous polyposis

FFPE

Formalin-fixed paraffin embedded

HEV

High endothelial venules

HRMA

High-resolution melting analysis

IHC

Immunohistochemistry

LN

Lymph node

NGS

Next-generation sequencing

PD(L)-1

Programmed death (ligand)-1

RTU

Ready-to-use

Treg

Regulatory T cells

TLO

Tertiary lymphoid organs

TME

Tumor microenvironment

Notes

Acknowledgements

The majority of human biological material used in this publication was provided by the Tumor bank, Antwerp University Hospital, Belgium, which is funded by the National Cancer Plan.

Author contributions

VS, EM and JJ designed the study and performed the data acquisition and analysis. CH processed the slides. KZ and SP performed the immunohistochemical staining. CH provided patient material. All authors contributed to the interpretation of the data, sample collection, drafting and revision of the manuscript.

Funding

The authors received no specific funding for this work.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflicts of interest.

Ethical approval and ethical standards

We received approval by the Ethics Committee of the Antwerp University Hospital/University of Antwerp (EC 18/45/517) to use historical samples. As it was a retrospective study, no informed consent of the patients could be obtained.

Supplementary material

262_2019_2390_MOESM1_ESM.pdf (314 kb)
Supplementary material 1 (PDF 314 kb)

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Copyright information

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

Authors and Affiliations

  • Vasiliki Siozopoulou
    • 1
    • 2
    Email author
  • Elly Marcq
    • 1
  • Julie Jacobs
    • 1
    • 2
  • Karen Zwaenepoel
    • 1
    • 2
  • Christophe Hermans
    • 1
    • 2
  • Jantine Brauns
    • 1
    • 2
  • Siegrid Pauwels
    • 2
  • Clément Huysentruyt
    • 3
  • Martin Lammens
    • 2
  • Johan Somville
    • 4
  • Evelien Smits
    • 1
    • 5
  • Patrick Pauwels
    • 1
    • 2
  1. 1.Center for Oncological ResearchUniversity of AntwerpAntwerpBelgium
  2. 2.Department of PathologyAntwerp University HospitalAntwerpBelgium
  3. 3.PAMM Laboratory for Pathology and Medical MicrobiologyCatharina HospitalEindhovenThe Netherlands
  4. 4.Department of Orthopedic SurgeryAntwerp University HospitalAntwerpBelgium
  5. 5.Center for Cell Therapy and Regenerative MedicineAntwerp University HospitalAntwerpBelgium

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