Immune Monitoring of the Circulation and the Tumor Microenvironment in Patients with Regionally Advanced Melanoma Receiving Neoadjuvant Ipilimumab

摘要: We evaluated neoadjuvant ipilimumab in patients with surgically operable regionally advanced melanoma order to define markers of activity the blood and tumor as assessed at baseline (before ipilimumab) early on-treatment. Patients were treated (10 mg/kg intravenously every 3 weeks ×2 doses) bracketing surgery. Tumor biospecimens obtained Flow cytometry immunohistochemistry for select biomarkers performed. Thirty five enrolled; IIIB (3; N2b), IIIC (32; N2c, N3), IV (2). Worst toxicities included Grade diarrhea/colitis (5; 14%), hepatitis (2; 6%), rash (1; 3%), elevated lipase 9%). Median follow up was 18 months: among 33 evaluable patients, median progression free survival (PFS) 11 months, 95% CI (6.2–19.2). There a significant decrease circulating myeloid derived suppressor cells (MDSC). Greater monocyte gate MDSC Lin1−/HLA-DR−/CD33+/CD11b+ associated improved PFS (p = 0.03). increase regulatory T (Treg; CD4+CD25hi+Foxp3+) that, unexpectedly, (HR 0.57; p 0.034). Baseline evidence fully activated type I CD4+ CD8+ antigen-specific cell immunity against cancer-testis (NY-ESO-1) melanocytic lineage (MART-1, gp100) antigens detected significantly potentiated after ipilimumab. In tumor, there 0.02). Ipilimumab induced increased infiltration by (CD69+) CD3+/CD4+ CD3+/CD8+ induction/potentiation memory (CD45RO+). The change Treg observed within showed an inverse relationship clinical benefit greater subset one year. Neoadjuvant evaluation revealed immunomodulating role on Treg, effector circulation microenvironment that warrants further pursuit quest optimizing immunotherapy.