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Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas

  • Lucie Duverger
  • Amélie Osio
  • Bernard Cribier
  • Laurent Mortier
  • Adèle De Masson
  • Nicole Basset-Seguin
  • Céleste Lebbé
  • Maxime BattistellaEmail author
Original Article
  • 90 Downloads

Abstract

Background

Adnexal carcinomas are rare and heterogeneous skin tumors, for which no standard treatments exist for locally advanced or metastatic tumors.

Aim of the study

To evaluate the expression of PD-L1 and CD8 in adnexal carcinomas, and to study the association between PD-L1 expression, intra-tumoral T cell CD8+ infiltrate, and metastatic evolution.

Materials and methods

Eighty-three adnexal carcinomas were included. Immunohistochemistry using anti-PD-L1 monoclonal antibodies (E1L3N and 22C3) and CD8 was performed. PD-L1 expression in tumor and immune cells, and CD8+ tumor-infiltrating lymphocyte (TIL) density were analyzed semi-quantitatively.

Results

Among the 60 sweat gland, 18 sebaceous and 5 trichoblastic carcinomas, 11% expressed PD-L1 in ≥ 1% tumor cells, more frequently sweat gland carcinomas (13%, 8/60) including apocrine carcinoma (40%, 2/5) and invasive extramammary Paget disease (57%, 4/7). Immune cells expressed significantly more PD-L1 than tumor cells (p < 0.01). Dense CD8+ TILs were present in 60% trichoblastic, 43% sweat gland, and 39% sebaceous carcinomas. CD8+ TILs were associated with PD-L1 expression by tumor cells (p < 0.01). Thirteen patients out of 47 developed metastases (27%) with a median follow-up of 30.5 months (range 7–36). Expression of PD-L1 by tumor cells was associated with the development of metastasis in univariate analysis (HR 4.0, 95% CI 1.1–15, p = 0.0377) but not in multivariate analysis (HR 4.1, 95% CI 0.6–29, p = 0.15).

Conclusion

PD-L1 expression is highly heterogeneous among adnexal carcinoma subtypes, higher in apocrine carcinoma and invasive extramammary Paget disease, and associated with CD8+ TILs. Our data suggest the interest of evaluating anti-PD1 immunotherapy in advanced or metastatic cutaneous adnexal carcinoma.

Keywords

Cutaneous adnexal carcinoma Programmed cell death ligand 1 (PD-L1) Tumor-infiltrating lymphocytes (TILs) CD8 

Abbreviations

AJCC

American Joint Committee on Cancer

APHP

Assistance Publique-Hôpitaux de Paris

BCC

Basal cell carcinoma

CHRU

Centre hospitalier régional universitaire

cSCC

Cutaneous squamous cell carcinoma

EMPD

Extramammary Paget disease

IC

Immune cells

NOS

No other specification

TC

Tumor cells

TMB

Tumor mutation burden

UMR

Unité mixte de recherche

WHO

World Health Organization

Notes

Acknowledgements

The authors thank the Tumorothèque of Saint Louis hospital for providing tissue material.

Author contributions

LD designed the study, acquired and analyzed data, drafted the work and revised it. AO acquired data and revised the work for important intellectual content. BC analyzed data and revised the work for important intellectual content. LM analyzed data and revised the work for important intellectual content. ADM acquired and analyzed data, did the statistical analysis, and revised the work for important intellectual content. NB-S acquired clinical data and revised the work for important intellectual content. CL acquired clinical data and revised the work for important intellectual content. MB designed the study, acquired and analyzed data, drafted the work, and revised the work for important intellectual content. All authors approved the final manuscript version.

Funding

No relevant funding.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

All patients were informed that part of the remaining tissue material could be used for research, and gave their consent according to the Helsinki declaration. Samples were obtained from the Tumorothèque of Saint-Louis Hospital (Tumor bank registration number DC2009.929, Ministry of Health, France).

Ethical standards

According to the bioethics French law of August 6th 2004, applicable at the time of the study, in the context of a retrospective monocentric non-interventional study, additional ethical committee approval was not necessary.

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Copyright information

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

Authors and Affiliations

  1. 1.Pathology Department, INSERM UMR_S1165Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (APHP)ParisFrance
  2. 2.Dermatology DepartmentHôpitaux universitaires de StrasbourgStrasbourgFrance
  3. 3.Dermatology DepartmentCentre Hospitalier Régional Universitaire (CHRU) de LilleLilleFrance
  4. 4.INSERM, Unité mixte de recherche (UMR)_S976University Paris DiderotParisFrance
  5. 5.Dermatology DepartmentHôpital St Louis, APHPParisFrance
  6. 6.INSERM, UMR_S1165University Paris DiderotParisFrance

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