Macrophage Response to Simulated Solar Radiation in the Development of Human Malignant Melanoma.

Autor:	Chu S; Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.; Western University of Health Sciences, College of Osteopathic Medicine of the Pacific, Northwest, Lebanon, OR, USA., Petukhova TA; Weill Cornell Medical College, New York, NY, USA., Bordeaux JS; Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., McCormick TS; Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Cooper KD; Department of Dermatology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Jazyk:	angličtina
Zdroj:	Archives of clinical & experimental dermatology [Arch Clin Exp Dermatol] 2021 Apr; Vol. 3 (1). Date of Electronic Publication: 2021 Apr 30.
DOI:	10.46527/2583-6374.119
Abstrakt:	Background: IFN-γ is widely debated regarding its purported anti- or pro-tumorigenic properties. We initiated a pilot study of primary malignant melanoma patients to investigate whether macrophage-derived IFN-γ is produced in humans as proposed in murine melanomagenesis models. Methods: Biopsy specimens of fresh-frozen primary melanoma tissue were used to quantify co-localization of IFN-γ, macrophages, lymphocytes, and downstream IFN-γ signatures. Additionally, we analyzed simulated solar radiation (SSR) exposed skin in patients with a history of melanoma versus healthy controls to compare the relative magnitude of macrophage infiltration. Results: Our data identified a subset of tumor infiltrating CD68 + macrophages that co-localized with IFN-γ (Pearson's Correlation = 0.33 ± 0.11) in patients with primary melanoma (Stage 0-III). Additionally, a population of infiltrating CD3 + lymphocytes strongly co-localized with IFN-γ (Pearson's Correlation = 0.57 ± 0.11). Malignant melanoma cells were double positive for downstream IFN-γ response elements, MIG/CXCL9, and phosphorylated STAT-1 (P-STAT-1). Cellular signaling pathways were also observed when we exposed the skin of melanoma patients to SSR. Despite robust CXCL9 expression in the epidermis of SSR-exposed skin of melanoma patients, we observed decreased macrophage infiltration into melanoma patient skin. Conclusion: Peritumoral macrophages in melanoma patient skin produce IFN-γ and melanocytes appear to exhibit in vivo responsiveness to IFN-γ, such as P-STAT-1 and upregulated CXCL9 expression. However, despite producing CXCL9 in response to SSR, the normal skin of melanoma patients demonstrates a weak leukocyte infiltration. Immune-modulatory studies for the prevention or treatment of human malignant melanoma may need to address complex tissue and melanocyte signaling and crosstalk. Competing Interests: Conflict of Interest Disclosures Authors declare no conflict of interests for this article.
Databáze:	MEDLINE
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