title: T-cell Landscape in a Primary Melanoma Predicts the Survival of Patients with Metastatic Disease after Their Treatment with Dendritic Cell Vaccines.
abstract: Tumor-infiltrating lymphocytes appear to be a predictor of survival in many cancers, including cutaneous melanoma. We applied automated multispectral imaging to determine whether density and distribution of T cells within primary cutaneous melanoma tissue correlate with survival of metastatic melanoma patients after dendritic cell (DC) vaccination. CD3(+) T cell infiltration in primary tumors from 77 metastatic melanoma patients was quantified using the ratio of intratumoral versus peritumoral T-cell densities (I/P ratio). Patients with longer survival after DC vaccination had stronger T-cell infiltration than patients with shorter survival in a discovery cohort of 19 patients (P = 0.000026) and a validation cohort of 39 patients (P = 0.000016). I/P ratio was the strongest predictor of survival in a multivariate analysis including M substage and serum lactate dehydrogenase level. To evaluate I/P ratio as a predictive biomarker, we analyzed 19 chemotherapy-treated patients. Longer survival times of DC-vaccinated compared with chemotherapy-treated patients was observed for high (P = 0.000566), but not low (P = 0.154) I/P ratios. In conclusion, T-cell infiltration into primary melanoma is a strong predictor of survival after DC vaccination in metastatic melanoma patients who, on average, started this therapy several years after primary tumor resection. The infiltration remains predictive even after adjustment for late-stage prognostic markers. Our findings suggest that the I/P ratio is a potential predictive biomarker for treatment selection. Cancer Res; 76(12); 3496-506. ©2016 AACR.
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands.
authors.forename: Angela
authors.initials: A
authors.lastname: Vasaturo
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Altuna
authors.initials: A
authors.lastname: Halilovic
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Kalijn F
authors.initials: KF
authors.lastname: Bol
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Dagmar I
authors.initials: DI
authors.lastname: Verweij
authors.affiliation: Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Willeke A M
authors.initials: WA
authors.lastname: Blokx
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, Amsterdam, the Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.affiliation: Department of Pathology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: J Han J M
authors.initials: JH
authors.lastname: van Krieken
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Theoretical Biology, Utrecht University, Utrecht, the Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Textor
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, the Netherlands. Carl.Figdor@radboudumc.nl.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
mesh_terms: D019496:Cancer Vaccines / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D009362:Neoplasm Metastasis; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
chemical_list: D019496:Cancer Vaccines