Purpose: To monitor the immune system of ipilimumab treated patients in order to investigate potential mechanisms of action that may correlate with treatment outcome.
Experimental Design: 103 blood samples from 43 patients with advanced melanoma were taken before, during and at the end of treatment. Hematological parameters were measured and multicolor flow cytometry analysis was performed in fresh samples within two hours of sample collection. Endpoints were clinical benefit and overall survival (OS).
Results: Strong differences in immune parameters such as CD25, CCR7 and CD15 in fresh and cryopreserved samples were observed. Treatment increased absolute lymphocyte counts, eosinophils and CD3+CD4+ICOS+ cells. Changes in CD4 memory populations were additionally observed, resulting in a frequency shift towards effector and central memory cells. Ipilimumab decreased frequencies of Tregs, polymorphonuclear MDSCs and production of suppressive mediators iNOS and arginase-1 by myeloid cells. Low monocytic MDSC frequencies after the first infusion were correlated with OS. At the end of treatment, an increase in CD8 effector memory T cells was correlated with clinical benefit and OS.
Conclusions: Analyzing immune parameters in fresh samples allows for accurate measurements of cell populations that are affected by cryopreservation. Ipilimumab treatment resulted in an overall activation of the immune system along with a diminished suppressive state. Patients who additionally had a decrease in monocytic MDSCs or an increase in CD8 effector memory T cells presented increased OS and clinical benefit. Measuring these parameters during ipilimumab treatment could provide insights on clinical responses and suggest modifications to the therapeutic approach.
Citation Format: Yago Pico De Coaña, Maria Wolodarski, Isabel Poschke, Yuya Yoshimoto, Giuseppe Masucci, Johan Hansson, Rolf Kiessling. MDSCs and CD8 effector memory T cells correlate with survival in melanoma patients treated with ipilimumab [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B026.