W193 - Peripheral Blood Immunophenotyping for Identification of Pre- and Post-treatment Immune Correlates of Checkpoint Inhibitor Response in Melanoma

Elisavet Ntavli – University College London; Lina Petersone – University College London; Chun Jing Wang – University College London; Astrid Fabri – University College London; Alexandros Kogimtzis – University College London; Vitalijs Ovcinnikovs – University College London; Ellen Ross – University College London; Frank Heuts – University College London; Yassin Elfaki – University College London; Luke Houghton – University College London; Toby Talbot – Royal Cornwall Hospitals NHS Trust; Amna Sheri – Royal Free London NHS Foundation Trust; Alexandra Pender – Royal Free London NHS Foundation Trust; David Chao – Royal Free London NHS Foundation Trust; Lucy Walker – University College London

Abstract Text: While checkpoint inhibitor therapies have revolutionized cancer treatment over the last decade, it has also become clear that efficacy varies greatly, with some patients showing complete responses whereas others are refractory to therapy. Robust biomarkers of response are currently lacking, thus we aimed to identify correlates of clinical response to the PD-1 blocking antibody pembrolizumab by immunophenotyping peripheral blood of patients with advanced malignant melanoma before and after treatment. We can demonstrate that response to PD-1 blockade was associated with increased expression of the proliferation marker Ki67, particularly in CD28+CD8 T cells. Meanwhile, individuals with progressive disease showed a transient increase in CTLA-4 expressing Treg and we can use ratios of activated and proliferating Treg to CD8 T cells to distinguish response following PD-1 blockade. Remarkably, using unsupervised clustering analysis of pre-treatment T cell subsets we can identify differences in individuals that responded to PD-1 blockade compared to individuals that did not. These differences mapped to expression of the proliferation marker Ki67 and the costimulatory receptor CD28 as well as the inhibitory molecules 2B4 and KLRG1. While these results require validation in larger patient cohorts, they suggest that flow cytometric analysis of a relatively small number of T cell markers in peripheral blood could provide a valuable tool for stratification of PD-1 blockade treatment response prior to therapy initiation. We are now expanding this approach to individuals treated with combination therapy of PD-1 and CTLA-4 blocking antibodies to understand how T cell populations relate to clinical response in this setting.