Research Papers:

This article has an addendum. Addendum in: Oncotarget. 2022; 13:1299-1299.

Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma

Julien Schaller, Hélène Maby-El Hajjami, Sylvie Rusakiewicz, Kalliopi Ioannidou, Nathalie Piazzon, Alexandra Miles, Déla Golshayan, Olivier Gaide, Daniel Hohl, Daniel E. Speiser and Karin Schaeuble _

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Oncotarget. 2021; 12:638-648. https://doi.org/10.18632/oncotarget.27915

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Julien Schaller1, Hélène Maby-El Hajjami1, Sylvie Rusakiewicz1, Kalliopi Ioannidou2, Nathalie Piazzon2, Alexandra Miles3, Déla Golshayan4, Olivier Gaide3, Daniel Hohl3, Daniel E. Speiser1 and Karin Schaeuble1

1 Department of Oncology, University Hospital Lausanne (CHUV/UNIL), Lausanne, Switzerland

2 Institute of Pathology, University Hospital Lausanne (CHUV), Lausanne, Switzerland

3 Department of Dermatology, University Hospital Lausanne (CHUV), Lausanne, Switzerland

4 Transplantation Center, University Hospital Lausanne (CHUV/UNIL), Lausanne, Switzerland

Correspondence to:

Karin Schaeuble,email: [email protected]

Keywords: lymphatic vessel; CD8+ T cell; perineural infiltration; skin squamous-cell carcinoma; tumor immunology

Received: July 30, 2020     Accepted: February 26, 2021     Published: March 30, 2021

Copyright: © 2021 Schaller et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy. The role of lymphatic vessels in skin squamous-cell carcinoma (sSCC), the second most common form of skin cancer, remains mostly unknown. Although anti-PD-1 therapy is beneficial for some patients with advanced sSCC, a greater understanding of disease mechanisms is still needed to develop better therapies.

Using quantitative multiplex immunohistochemistry, we analyzed sSCC sections from 36 patients. CD8+ T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8+ T cell density in tumor areas. An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density. Since both, metastasis and perineural infiltration are known to affect tumor progression and patients’ prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. Our data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma.

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