{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332987/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332987"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Neoadjuvant Pepinemab with Immune Checkpoint Blockade Remodels the Tumor Microenvironment in Metastatic Melanoma","description":"Neoadjuvant 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.","dates":{"publication":"2026/08/20"},"accession":"GSE332987","cross_references":{"GSM":["GSM9756709","GSM9756736","GSM9756714","GSM9756715","GSM9756712","GSM9756734","GSM9756735","GSM9756713","GSM9756718","GSM9756719","GSM9756716","GSM9756717","GSM9756732","GSM9756710","GSM9756733","GSM9756711","GSM9756730","GSM9756731","GSM9756703","GSM9756725","GSM9756726","GSM9756704","GSM9756723","GSM9756701","GSM9756724","GSM9756702","GSM9756729","GSM9756707","GSM9756708","GSM9756727","GSM9756705","GSM9756706","GSM9756728","GSM9756721","GSM9756700","GSM9756722","GSM9756720"],"GPL":["24676"],"GSE":["332987"],"taxon":["Homo sapiens"]}}