{"doi":"10.1016/j.xjidi.2023.100255","title":"Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade","abstract":"The immune checkpoint ligand PD-L1 has emerged as a molecular target for skin cancer therapy and might also hold promise for preventive intervention targeting solar UV light-induced skin damage. In this study, we have explored the role of PD-L1 in acute keratinocytic photodamage testing the effects of small-molecule pharmacological inhibition. Epidermal PD-L1 upregulation in response to chronic photodamage was established using immunohistochemical and proteomic analyses of a human skin cohort, consistent with earlier observations that PD-L1 is upregulated in cutaneous squamous cell carcinoma. Topical application of the small-molecule PD-L1 inhibitor BMS-202 significantly attenuated UV-induced activator protein-1 transcriptional activity in SKH-1 bioluminescent reporter mouse skin, also confirmed in human HaCaT reporter keratinocytes. RT-qPCR analysis revealed that BMS-202 antagonized UV induction of inflammatory gene expression. Likewise, UV-induced cleavage of procaspase-3, a hallmark of acute skin photodamage, was attenuated by topical BMS-202. NanoString nCounter transcriptomic analysis confirmed downregulation of cutaneous innate immunity- and inflammation-related responses, together with upregulation of immune response pathway gene expression. Further mechanistic analysis confirmed that BMS-202 antagonizes UV-induced PD-L1 expression both at the mRNA and protein levels in SKH-1 epidermis. These data suggest that topical pharmacological PD-L1 antagonism using BMS-202 shows promise for skin protection against photodamage.","journal":"JID Innovations","year":2024,"id":453171,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9555,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":958463,"name":"Prajakta Vaishampayan","orcid":"0009-0003-0356-7061","position":1,"is_corresponding":false},{"id":330826,"name":"Jana Jandová","orcid":"0000-0002-9100-9574","position":2,"is_corresponding":false},{"id":1275729,"name":"Yuchen Ai","orcid":"0009-0007-3484-6927","position":3,"is_corresponding":false},{"id":1275730,"name":"Viktoria Kirschnerova","orcid":"0000-0001-8810-1321","position":4,"is_corresponding":false},{"id":1194146,"name":"Tianshun Zhang","orcid":"0000-0001-7018-8393","position":5,"is_corresponding":false},{"id":411038,"name":"Valerie Calvert","orcid":"0000-0002-5075-7728","position":6,"is_corresponding":false},{"id":406272,"name":"Emanuel F. Petricoin","orcid":"0000-0001-8787-5990","position":7,"is_corresponding":false},{"id":713921,"name":"H.‐H. Sherry Chow","orcid":"0000-0002-9638-711X","position":8,"is_corresponding":false},{"id":418076,"name":"Chengcheng Hu","orcid":"0000-0001-8525-0356","position":9,"is_corresponding":false},{"id":337069,"name":"Denise J. Roe","orcid":"0000-0001-6989-6579","position":10,"is_corresponding":false},{"id":134899,"name":"Ann M. Bode","orcid":null,"position":11,"is_corresponding":false},{"id":452909,"name":"Clara Curiel‐Lewandrowski","orcid":"0000-0001-8982-6252","position":12,"is_corresponding":false},{"id":330827,"name":"Georg T. Wondrak","orcid":"0000-0003-4799-8608","position":13,"is_corresponding":false},{"id":526636,"name":"Sally E. Dickinson","orcid":"0000-0002-2049-543X","position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-07-19T02:02:58.784290Z","pmid":"38328594","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":[]}