1177 Elucidating the immune landscape of immune related adverse events to checkpoint inhibitors

• DOI: 10.1136/jitc-2024-sitc2024.1177
• Publication Date: 2024-11-05T14:58:54Z
• Authors: Marta Velasco San...; Benedetta Albieri; Maria Charlotte K...; Inge Mansfield No...; Rebecca Jurlander; Joel Emanuel Jörn; Anders Kverneland; Inge Marie Svane
• Keywords: Immune checkpoint

<h3>Background</h3> Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by enhancing the immune system's ability to recognize and attack tumors. However, their use is frequently accompanied immune-related adverse events (irAEs), which can significantly impact patient quality of life necessitate discontinuation. Moreover, only few studies been focused on management these irAEs. The current strategy consists primarily corticosteroids, are immunosuppressive drugs that also affect efficacy ICIs. In this study, we aim at elucidating underlying mechanisms irAEs using flow cytometry analysis fresh blood samples from patients undergoing ICI therapy. Better understanding support more targeted strategies. <h3>Methods</h3> We collected receiving ICIs multiple time points, including before treatment, during onset irAEs, Samples were analyzed fresh, within 1–2 hours after collection. Using cytometry, performed comprehensive immunophenotyping identify changes in various cell populations, T-cells, B-cells, natural killer cells, different monocytic populations. Data was conducted through unsupervised clustering with FlowSOM package R, followed dimensionality reduction UMAP, enabling identification distinct immunological profiles associated development <h3>Results</h3> <h3>Conclusions</h3> Flow showed an increase CD38⁺ HLA-DR⁺ EM T-cells while antibody-producing B-cells increased same subsets upregulated responders management, opposite a lower frequency monocytes compared non-responders. Understanding cellular level provides crucial insights into potential strategies for mitigating thereby improving outcomes immunotherapy. This research paves way developing personalized optimizing therapeutic index ICIs, safety clinical practice.