GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332987/primary200OKTranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332987GEOGSEfalseNeoadjuvant Pepinemab with Immune Checkpoint Blockade Remodels the Tumor Microenvironment in Metastatic MelanomaNeoadjuvant immune checkpoint inhibitors (ICIs) improve event-free survival in metastatic melanoma, yet resistance and recurrence remain common. We evaluated pepinemab, a Semaphorin 4D (SEMA4D)–blocking antibody, in combination with nivolumab and/or ipilimumab in a phase II neoadjuvant biomarker trial for patients with resectable metastatic melanoma. Patients received two neoadjuvant doses followed by curative-intent surgery and one year of adjuvant nivolumab. Pepinemab-containing regimens did not increase immune-related adverse events and did not delay or preclude curative-intent surgical resection. Mechanistically, pepinemab plus ICI was associated with immune remodeling features, including increased T and B cell infiltration and enrichment of type 1 conventional dendritic cells. These changes were associated with the formation of mature lymphoid aggregates resembling tertiary lymphoid structures that contained clonally expanded T cell receptor repertoires, consistent with localized cytotoxic activity. Together, these findings support further evaluation of SEMA4D blockade as a strategy to enhance neoadjuvant immunotherapy in melanoma.2026/08/20GSE332987GSM9756709GSM9756736GSM9756714GSM9756715GSM9756712GSM9756734GSM9756735GSM9756713GSM9756718GSM9756719GSM9756716GSM9756717GSM9756732GSM9756710GSM9756733GSM9756711GSM9756730GSM9756731GSM9756703GSM9756725GSM9756726GSM9756704GSM9756723GSM9756701GSM9756724GSM9756702GSM9756729GSM9756707GSM9756708GSM9756727GSM9756705GSM9756706GSM9756728GSM9756721GSM9756700GSM9756722GSM975672024676332987Homo sapiens