{"doi":"10.46527/2583-6374.119","title":"Macrophage Response to Simulated Solar Radiation in the Development of Human Malignant Melanoma","abstract":"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: 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.","journal":"Archives of Clinical & Experimental Dermatology","year":2021,"id":212661,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":803732,"name":"Tatyana A. Petukhova","orcid":null,"position":1,"is_corresponding":false},{"id":441927,"name":"Jeremy S. Bordeaux","orcid":"0000-0002-7010-7730","position":2,"is_corresponding":false},{"id":376945,"name":"Thomas S. McCormick","orcid":"0000-0002-3294-0326","position":3,"is_corresponding":false},{"id":441928,"name":"Kevin D. Cooper","orcid":"0000-0002-1986-3602","position":4,"is_corresponding":false},{"id":677221,"name":"Sherman Chu","orcid":"0000-0002-4750-8958","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-18T23:52:27.434608Z","pmid":"37309359","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}