TY - JOUR T1 - Neoadjuvant PROSTVAC prior to radical prostatectomy enhances T-cell infiltration into the tumor immune microenvironment in men with prostate cancer JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-000655 VL - 8 IS - 1 SP - e000655 AU - Houssein Abdul Sater AU - Jennifer L Marté AU - Renee N Donahue AU - Beatriz Walter-Rodriguez AU - Christopher R Heery AU - Seth M Steinberg AU - Lisa M Cordes AU - Guinevere Chun AU - Fatima Karzai AU - Marijo Bilusic AU - Stephanie A Harmon AU - Ismail Baris Turkbey AU - Peter L Choyke AU - Jeffrey Schlom AU - William L Dahut AU - Ravi A Madan AU - Peter A Pinto AU - James L Gulley Y1 - 2020/03/01 UR - http://jitc.bmj.com/content/8/1/e000655.abstract N2 - Background Clinical trials have shown the ability of therapeutic vaccines to generate immune responses to tumor-associated antigens (TAAs). What is relatively less known is if this translates into immune-cell (IC) infiltration into the tumor microenvironment. This study examined whether neoadjuvant prostate-specific antigen (PSA)-targeted vaccination with PROSTVAC could induce T-cell immunity, particularly at the tumor site.Methods An open-label, phase II study of neoadjuvant PROSTVAC vaccine enrolled 27 patients with localized prostate cancer awaiting radical prostatectomy (RP). We evaluated increases in CD4 and CD8 T-cell infiltrates (RP tissue vs baseline biopsies) using a six-color multiplex immunofluorescence Opal method. Antigen-specific responses were assessed by intracellular cytokine staining after in vitro stimulation of peripheral blood mononuclear cells with overlapping 15-mer peptide pools encoding the TAAs PSA, brachyury and MUC-1.Results Of 27 vaccinated patients, 26 had matched prevaccination (biopsy) and postvaccination (RP) prostate samples available for non-compartmentalized analysis (NCA) and compartmentalized analysis (CA). Tumor CD4 T-cell infiltrates were significantly increased in postvaccination RP specimens compared with baseline biopsies by NCA (median 176/mm² vs 152/mm²; IQR 136–317/mm² vs 69–284/mm²; p=0.0249; median ratio 1.20; IQR 0.64–2.25). By CA, an increase in both CD4 T-cell infiltrates at the tumor infiltrative margin (median 198/mm² vs 151/mm²; IQR 123–500/mm² vs 85–256/mm²; p=0.042; median ratio 1.44; IQR 0.59–4.17) and in CD8 T-cell infiltrates at the tumor core (median 140/mm² vs 105/mm²; IQR 91–175/mm² vs 83–163/mm²; p=0.036; median ratio 1.25; IQR 0.88–2.09) were noted in postvaccination RP specimens compared with baseline biopsies. A total of 13/25 patients (52%) developed peripheral T-cell responses to any of the three tested TAAs (non-neoantigens); five of these had responses to more than one antigen of the three evaluated.Conclusion Neoadjuvant PROSTVAC can induce both tumor immune response and peripheral immune response.Trial registration number NCT02153918. ER -