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Article

Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development

by
Sokchea Khou
1,†,
Alexandra Popa
1,2,†,
Carmelo Luci
1,3,‡,
Franck Bihl
1,‡,
Aida Meghraoui-Kheddar
1,
Pierre Bourdely
1,4,
Emie Salavagione
1,
Estelle Cosson
1,
Alain Rubod
1,
Julie Cazareth
1,
Pascal Barbry
1,
Bernard Mari
1,
Roger Rezzonico
1,
Fabienne Anjuère
1 and
Veronique M. Braud
1,*
1
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique, Université Côte d’Azur, UMR7275, 06560 Valbonne, Sophia Antipolis, France
2
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
3
C3M, INSERM U1065, Université Côte d’Azur, 06204 Nice, France
4
Laboratory of Phagocyte Immunobiology, Peter Gorer Department of Immunobiology, Centre for Inflammation Biology and Cancer Immunology, King’s College London, London SE1 1UL, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to the work as first authors.
‡
These authors contributed equally to the work as second authors.
Cancers 2020, 12(7), 1860; https://doi.org/10.3390/cancers12071860
Submission received: 11 June 2020 / Revised: 6 July 2020 / Accepted: 8 July 2020 / Published: 10 July 2020
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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Abstract

Cutaneous squamous cell carcinoma (cSCC) development has been linked to immune dysfunctions but the mechanisms are still unclear. Here, we report a progressive infiltration of tumor-associated neutrophils (TANs) in precancerous and established cSCC lesions from chemically induced skin carcinogenesis. Comparative in-depth gene expression analyses identified a predominant protumor gene expression signature of TANs in lesions compared to their respective surrounding skin. In addition, in vivo depletion of neutrophils delayed tumor growth and significantly increased the frequency of proliferating IFN-γ (interferon-γ)-producing CD8+ T cells. Mechanisms that limited antitumor responses involved high arginase activity, production of reactive oxygen species (ROS) and nitrite (NO), and the expression of programmed death-ligand 1 (PD-L1) on TAN, concomitantly with an induction of PD-1 on CD8+ T cells, which correlated with tumor size. Our data highlight the relevance of targeting neutrophils and PD-L1-PD-1 (programmed death-1) interaction in the treatment of cSCC.
Keywords: neutrophils; cutaneous squamous cell carcinoma; PD-1; PD-L1; gene expression profile neutrophils; cutaneous squamous cell carcinoma; PD-1; PD-L1; gene expression profile
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MDPI and ACS Style

Khou, S.; Popa, A.; Luci, C.; Bihl, F.; Meghraoui-Kheddar, A.; Bourdely, P.; Salavagione, E.; Cosson, E.; Rubod, A.; Cazareth, J.; et al. Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development. Cancers 2020, 12, 1860. https://doi.org/10.3390/cancers12071860

AMA Style

Khou S, Popa A, Luci C, Bihl F, Meghraoui-Kheddar A, Bourdely P, Salavagione E, Cosson E, Rubod A, Cazareth J, et al. Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development. Cancers. 2020; 12(7):1860. https://doi.org/10.3390/cancers12071860

Chicago/Turabian Style

Khou, Sokchea, Alexandra Popa, Carmelo Luci, Franck Bihl, Aida Meghraoui-Kheddar, Pierre Bourdely, Emie Salavagione, Estelle Cosson, Alain Rubod, Julie Cazareth, and et al. 2020. "Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development" Cancers 12, no. 7: 1860. https://doi.org/10.3390/cancers12071860

APA Style

Khou, S., Popa, A., Luci, C., Bihl, F., Meghraoui-Kheddar, A., Bourdely, P., Salavagione, E., Cosson, E., Rubod, A., Cazareth, J., Barbry, P., Mari, B., Rezzonico, R., Anjuère, F., & Braud, V. M. (2020). Tumor-Associated Neutrophils Dampen Adaptive Immunity and Promote Cutaneous Squamous Cell Carcinoma Development. Cancers, 12(7), 1860. https://doi.org/10.3390/cancers12071860

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