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.
Highlights
Cutaneous squamous cell carcinoma is the second most common non-melanoma skin cancer, which is associated with alterations in immunity that favor inflammation and tumor development [1].cSCCs are generally cured with surgery, but they can reach a stage of advanced invasive disease associated with extremely rapid local relapse, for which no efficient therapy has been approved so far.Antitumor activities of immune cells have been shown to be central to immune surveillance of the Cancers 2020, 12, 1860; doi:10.3390/cancers12071860 www.mdpi.com/journal/cancersCancers 2020, 12, 1860 skin
To assess the role of tumor-associated neutrophils (TANs) in cSCC, we focused our study on Gr-1bright /Ly6G+ neutrophils that extravagated into tissue, either within the skin surrounding precancerous lesions and established carcinomas, or those infiltrating the precancerous lesions and carcinomas
We purified these neutrophils by flow cytometry (Figure S1B) and performed unbiased gene expression array analysis to investigate their molecular signatures throughout cSCC development
Summary
Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer, which is associated with alterations in immunity that favor inflammation and tumor development [1].cSCCs are generally cured with surgery, but they can reach a stage of advanced invasive disease associated with extremely rapid local relapse, for which no efficient therapy has been approved so far.Antitumor activities of immune cells have been shown to be central to immune surveillance of the Cancers 2020, 12, 1860; doi:10.3390/cancers12071860 www.mdpi.com/journal/cancersCancers 2020, 12, 1860 skin. Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer, which is associated with alterations in immunity that favor inflammation and tumor development [1]. 12-myristate 13-acetate) skin carcinogenesis in CXCR2−/− (C-X-C motif chemokine receptor 2) mice suggests that myeloid suppressor cells play a role, but their full characterization has not been done yet [5]. This is consistent with high-risk cSCC patients harboring an increased number of circulating and tumor-resident neutrophils [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
