Abstract A016: T cell landscape within primary melanoma as a predictive biomarker of survival after cancer vaccination in patients with metastatic disease
Authors: Vasaturo Angela , Halilovic Altuna , Bol Kalijn , Verweij Dagmar , Groenen Patricia , Krieken Han van , Blokx Willeke , Vries Jolanda de , Textor Johannes , Figdor Carl G. 
Published: May 2016

Melanoma is a highly malignant melanocyte-derived tumor and its incidence is increasing at outstanding rate. Despite different types of immunotherapy became available for the treatment of melanoma, including adoptive T cell transfer, immune checkpoint blockade, and vaccines such as dendritic cell vaccines, when applied to treat metastatic melanoma, only 10 to 40% of the patients have long term benefit. Furthermore, given the toxicity and high costs associated with immunotherapy there is a stringent need to identify biomarkers that may predict its potential efficacy. We have investigated whether the presence and distribution of T cells within the primary tumor of melanoma patients correlates with survival when treated for metastatic disease with dendritic cell based cancer vaccines.

Multispectral imaging and quantitative immunohistochemistry have been used to compare the tumor microenvironment of responding patients, that survived longer than 20 months after immunotherapy, and non-responding patients that survived less than 12 months after immunotherapy. The density and location of T cell were initially assessed in primary melanomas of 19 metastatic melanoma patients treated with dendritic cell based immunotherapy (discovery set) and subsequently in an independent cohort of 39 patients (validation cohort). In the discovery cohort we observed a very high correlation between the ratios of peritumoral over intratumoral T cells in the primary tumor and overall survival; lower peri/intratumoral T cell ratios in primary tumors were associated with improved clinical outcome indicating that the intratumoral T cell component is more prominent in responding patients whereas T cells fail to infiltrate the tumor in non-responding patients. ROC curve and multivariate analysis were exploited to evaluate the predictive power of the T cell ratio compared and/or combined to established prognostic markers. The same statistical analyses in the validation cohort confirmed our findings showing that the peri/intratumoral T cell ratio correctly predicted long term survival after DC vaccination in 90% of the cases and was the strongest predictor of survival in the multivariate analysis. This study indicates that the ratio between CD3 positive peri/intra-tumoral T cells is a very strong predictor of clinical outcome and response to dendritic cells immunotherapy in melanoma patients.

Citation Format: Angela Vasaturo, Altuna Halilovic, Kalijn Bol, Dagmar Verweij, Patricia Groenen, Han van Krieken, Willeke Blokx, Jolanda de Vries, Johannes Textor, Carl G. Figdor. T cell landscape within primary melanoma as a predictive biomarker of survival after cancer vaccination in patients with metastatic disease. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A016.