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

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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.

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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

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Acknowledgements

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

Funding

No relevant funding.

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Authors and Affiliations

  1. Pathology Department, INSERM UMR_S1165, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris (APHP), 1 Avenue Claude Vellefaux, 75010, Paris, France

    Lucie Duverger, Amélie Osio & Maxime Battistella

  2. Dermatology Department, Hôpitaux universitaires de Strasbourg, Strasbourg, France

    Bernard Cribier

  3. Dermatology Department, Centre Hospitalier Régional Universitaire (CHRU) de Lille, Lille, France

    Laurent Mortier

  4. INSERM, Unité mixte de recherche (UMR)_S976, University Paris Diderot, Paris, France

    Adèle De Masson, Nicole Basset-Seguin & Céleste Lebbé

  5. Dermatology Department, Hôpital St Louis, APHP, Paris, France

    Adèle De Masson, Nicole Basset-Seguin & Céleste Lebbé

  6. INSERM, UMR_S1165, University Paris Diderot, Paris, France

    Maxime Battistella

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  1. Lucie Duverger
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  2. Amélie Osio
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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.

Corresponding author

Correspondence to Maxime Battistella.

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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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Duverger, L., Osio, A., Cribier, B. et al. Heterogeneity of PD-L1 expression and CD8 tumor-infiltrating lymphocytes among subtypes of cutaneous adnexal carcinomas. Cancer Immunol Immunother 68, 951–960 (2019). https://doi.org/10.1007/s00262-019-02334-8

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