Journal
CANCERS
Volume 12, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/cancers12071860
Keywords
neutrophils; cutaneous squamous cell carcinoma; PD-1; PD-L1; gene expression profile
Categories
Funding
- French National Agency, ANR through the Investments for the Future [LABEX SIGNALIFE: ANR-11-LABX-0028-01]
- CANCEROPOLE PACA
- CENTRENATIONAL DE LA RECHERCHE SCIENTIFIQUE
- INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
- UNIVERSITE COTE D'AZUR
- REGION PROVENCE-ALPES-COTE D'AZUR
- FONDATION ARC pour la recherche sur le Cancer
- FONDATION DE L'AVENIR
- LIGUENATIONALE CONTRE LE CANCER
- FONDATION D'ENTREPRISE SILAB JEAN PAUFIQUE
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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-gamma (interferon-gamma)-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.
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