Abstract LB-116: Myeloid derived suppressor cells and NK cells are correlated with clinical benefit and survival in advanced melanoma patients treated with PD-1 blocking antibodies nivolumab and pembrolizumab
Authors: Coaña Yago Pico De , Wolodarski Maria , Avila Irene van der Haar , Masucci Giuseppe V. , Hansson Johan , Kiessling Rolf 
Published: August 2018

Abstract
Blockade of the PD-1 receptor has revolutionized the treatment of metastatic melanoma, with significant increases in overall survival, and a dramatic improvement in patient quality of life. Despite the success of this therapeutic approach, the number of responding patients is limited and there is a need for predictive biomarkers and a deeper mechanistic analysis of the cellular populations involved in a clinical response. With this objective in mind, an in-depth immune monitoring study was conducted in advanced melanoma patients undergoing treatment with pembrolizumab or nivolumab.
29 patients receiving pembrolizumab (n=5) or nivolumab (n=24) treatment at Karolinska University Hospital were included in this study. Blood samples were collected from patients at the following time points: Before treatment and at the time of the second and fourth doses. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation and stained for flow cytometric analysis within two hours of sample collection.
In the 29 patients included, median OS was 884 days from the start of treatment. Adverse events were observed in 18 patients (62%), including three grade 3-4 (10%). Patients were classified according to their response as PD (progressive disease, 45%), SD (stable disease, 3%) MR (mixed response, 7%) PR (partial response, 31%) and CR (complete response, 14%). For analytic purposes, patients were divided into two groups: 19 (59%) patients with clinical benefit (includes responders and patients with stable disease) and no clinical benefit (12 patients with progressive disease). Patients with clinical benefit had a median overall survival (MOS) of 1013 days, significantly longer than the 303 day MOS in the no clinical benefit group.
After analyzing the patients PBMC with a broad flow cytometry panel that included major immune subsets (T cells, NK cells, dendritic cells and myeloid derived suppressor cells (MDSCs)), our results showed that, before treatment, the frequency of two populations is related to clinical benefit: On one hand, patients with clinical benefit had significantly lower frequencies of monocytic MDSCs. On the other hand, NK cell frequencies were higher in these patients. Furthermore, Kaplan Meier analysis showed that patients with high frequencies of NK cells had significantly longer MOS times when compared to patients with low NK cell frequencies. Similarly, patients with low frequencies of monocytic MDSCs, showed significantly better MOS.
Our results suggest that cellular populations other than T cells can be critical in the outcome of PD-1 blockade treatment. Specifically, the frequencies of NK cells and monocytic MDSCs are correlated with survival and clinical benefit and their role as predictive biomarkers should be further evaluated.
Citation Format: Yago Pico De Coaña, Maria Wolodarski, Irene van der Haar Avila, Giuseppe V. Masucci, Johan Hansson, Rolf Kiessling. Myeloid derived suppressor cells and NK cells are correlated with clinical benefit and survival in advanced melanoma patients treated with PD-1 blocking antibodies nivolumab and pembrolizumab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-116.