biostudies-literatureDavar DNCI NIH HHSNIH HHS1898-1918.e12https://www.ebi.ac.uk/biostudies/studies/S-EPMC11560503biostudies-literatureUnknown42(11)Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8⁺ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67⁺CD8⁺ T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activatiCancer cellNeoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial.PMC11560503P50 CA254865U01 CA268806P30 CA047904S10 OD028483R01 CA257265U01 CA271407R01 CA222203McCulloch JAKim SWKrieg AMO'Toole JPSridharan SSHoltzman MPNajjar YGWang HMauro DKirkwood JMSingh JTrinchieri GFury MGSun JWooldridge JFang JRDzutsev AKDuvvuri UPark HJAmatore FDeBlasio RFernandes MRMorrison RMPaulovich AGJin YPagliano OLuke JJBobilev DDas Neves RXGao WBadger JHRodrigues RRAggarwal PChauvin JMPingpank JFDing QDeutsch JSZarour HMZhao LDavar DUrban CDivarkar PWhiteaker JRHartman DJDeitrick CTaube JMBai YCole AMGroetsch CBao RRose AKarunamurthy AA Choudry HfalseNeoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial.Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8⁺ tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67⁺CD8⁺ T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activati2024-01-01T00:00:00Z2024 Nov2026-06-06T15:44:19.644Z2026-06-02T03:09:21.859ZS-EPMC115605033948641110.1016/j.ccell.2024.10.007