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

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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.

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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

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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.

Funding

The authors received no specific funding for this work.

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Authors and Affiliations

  1. Center for Oncological Research, University of Antwerp, Antwerp, Belgium

    Vasiliki Siozopoulou, Elly Marcq, Julie Jacobs, Karen Zwaenepoel, Christophe Hermans, Jantine Brauns, Evelien Smits & Patrick Pauwels

  2. Department of Pathology, Antwerp University Hospital, Wilrijkstraat 10, Edegem, 2650, Antwerp, Belgium

    Vasiliki Siozopoulou, Julie Jacobs, Karen Zwaenepoel, Christophe Hermans, Jantine Brauns, Siegrid Pauwels, Martin Lammens & Patrick Pauwels

  3. PAMM Laboratory for Pathology and Medical Microbiology, Catharina Hospital, Eindhoven, The Netherlands

    Clément Huysentruyt

  4. Department of Orthopedic Surgery, Antwerp University Hospital, Antwerp, Belgium

    Johan Somville

  5. Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium

    Evelien Smits

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  1. Vasiliki Siozopoulou
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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.

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Correspondence to Vasiliki Siozopoulou.

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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.

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Siozopoulou, V., Marcq, E., Jacobs, J. et al. Desmoid tumors display a strong immune infiltration at the tumor margins and no PD-L1-driven immune suppression. Cancer Immunol Immunother 68, 1573–1583 (2019). https://doi.org/10.1007/s00262-019-02390-0

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