Abstract A14: Surgical removal of metastatic lesions increases T-cell reactivity to tumor-associated antigens in stage III melanoma patients

Abstract

Currently, there are hardly any peripheral blood biomarkers that allow for identification of patients’ prognosis or survival in advanced melanoma patients. Our main objective was to compare the reactivity of peripheral blood T cells of patients with stage III or IV metastatic melanoma to Tumor-Associated Antigens, before and after surgery where metastatic lesions were removed. Peripheral blood mononuclear cells were isolated from blood samples taken before and after surgery and were stimulated over the course of two weeks with overlapping peptide pools of three known melanoma antigens: MelanA, NY-ESO-1, and Cripto-1. After 12 days, cells were re-stimulated and analyzed using multicolor flow cytometry. CD4 and CD8 positive cells were analyzed for cytokine production. McNemar’s test was used to analyze changes before and after surgery, and correlation between cell reactivity and cytokine production with progression free survival was determined by Kaplan Meier analysis. Surgical removal of metastatic lesions changed reactivity of T cells to MelanA, NY-ESO-1 and Cripto-1. The presence of CD4 T cells that produced IL-17 and/or TNF-a after stimulation was correlated with a worse progression-free survival (PFS). We show here that surgical removal of metastases increases T-cell reactivity in melanoma patients and that certain cytokine profiles may be associated to PFS. This could provide insight into the complexity of the correlation between a specific T-cell response and a favorable immune response to metastatic melanoma. Citation Format: Yago Pico de Coana, Friða Bjork Gunnarsdottir, Maria Wolodarski, Suzanne Egyhazi Brage, Giuseppe Masucci, Johan Hansson, Rolf Kiessling. Surgical removal of metastatic lesions increases T-cell reactivity to tumor-associated antigens in stage III melanoma patients [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A14.