{"doi":"10.1093/oncolo/oyaf327","title":"Pathomic immune biomarkers define recurrence risk in early-stage melanoma","abstract":"BACKGROUND: There is an urgent need for biomarkers in early-stage melanoma because the benefit of adjuvant immunotherapy is marginal while the toxicity is considerable. Immune surveillance is a key mechanism limiting melanoma progression, but no immune biomarkers have yet been sufficiently validated for clinical use. METHODS: We validate 3 digital pathology biomarkers, all previously trained in published cohorts and testable in formalin fixed paraffin embedded specimens, for correlation with recurrence free survival and distant metastatic free survival: (1) tumor infiltrating lymphocytes identified using artificial intelligence in digital images (eTILs), (2) nanoString melanoma immune profile (MIP), and (3) quantitative immunofluorescence of CD8+ cells. RESULTS: Three immune biomarkers were validated and found to correlate with recurrence at 36 months by receiver operating curve analysis (eTILs area under the curve [AUC] = 0.706, P = .002; MIP AUC = 0.775, P < .001; and CD8% AUC = 0.682, P = .009) and define high and low risk groups using Kaplan Meier (KM) curves within the IIA-IIID population (P = .007 for eTILs and P < .001 for MIP and CD8%) and within the difficult to treat IIB-IIIA subset (P = .005, P < .001, P < .001, respectively). Immune biomarkers enhance clinical predictors (P = .012, P < .001, P = .004), and correlate with distant metastatic recurrence (P = .031, P = .047, P = .014, respectively). Network analysis shows that stage and depth combined with pathomic immune features yields the highest correlation with recurrence (AUC = 0.875, P < .001). CONCLUSIONS: Immune biomarkers should be prospectively validated in stage II-III melanoma for the purpose of avoiding overtreatment of low-risk patients and to stratify high-risk patients for clinical trials.","journal":"The Oncologist","year":2025,"id":534946,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1367848,"name":"Ajay Singh","orcid":"0000-0003-4969-7681","position":1,"is_corresponding":false},{"id":1418571,"name":"Gerardo Espinoza","orcid":null,"position":2,"is_corresponding":false},{"id":1418088,"name":"Chenxin Zhang","orcid":"0000-0002-4518-1322","position":3,"is_corresponding":false},{"id":1418572,"name":"Tianyun Jiang","orcid":null,"position":4,"is_corresponding":false},{"id":1177522,"name":"Divya Kenchappa","orcid":null,"position":5,"is_corresponding":false},{"id":1372144,"name":"Yadriel Bracero","orcid":"0009-0002-6483-4867","position":6,"is_corresponding":false},{"id":1219094,"name":"Swanand Rakhade","orcid":null,"position":7,"is_corresponding":false},{"id":651494,"name":"Sharmin Sultana","orcid":"0000-0002-2398-3500","position":8,"is_corresponding":false},{"id":1418573,"name":"Suryansh Shukla","orcid":null,"position":9,"is_corresponding":false},{"id":1411898,"name":"Emily Nghiem","orcid":"0009-0001-5157-7198","position":10,"is_corresponding":false},{"id":1418089,"name":"Matteo Abbruzzese","orcid":"0000-0002-5041-8056","position":11,"is_corresponding":false},{"id":245836,"name":"Chaoyuan Kuang","orcid":"0000-0002-8984-3906","position":12,"is_corresponding":false},{"id":488590,"name":"Larisa J. Geskin","orcid":"0000-0001-7348-2571","position":13,"is_corresponding":false},{"id":447101,"name":"David Entenberg","orcid":"0000-0003-0422-7264","position":14,"is_corresponding":false},{"id":409101,"name":"Robyn D. Gartrell","orcid":"0000-0003-3287-4223","position":15,"is_corresponding":false},{"id":706115,"name":"Tammie Ferringer","orcid":"0000-0001-9701-5265","position":16,"is_corresponding":false},{"id":956855,"name":"Lawrence W. Leung","orcid":"0000-0003-3333-3242","position":17,"is_corresponding":false},{"id":218544,"name":"Jee‐Young Moon","orcid":"0000-0001-9218-8335","position":18,"is_corresponding":false},{"id":485751,"name":"Basil A. Horst","orcid":null,"position":19,"is_corresponding":false},{"id":375552,"name":"Kent L. Nastiuk","orcid":null,"position":20,"is_corresponding":false},{"id":109014,"name":"David L. Rimm","orcid":"0000-0001-5820-4397","position":21,"is_corresponding":false},{"id":1182373,"name":"Rui Chang","orcid":"0009-0000-5823-4799","position":22,"is_corresponding":false},{"id":409107,"name":"Yvonne M. Saenger","orcid":"0000-0001-7074-2681","position":23,"is_corresponding":false},{"id":623098,"name":"Thazin Nwe Aung","orcid":"0000-0003-4150-0426","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T02:51:52.019261Z","pmid":"41052286","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":[]}