Abstract 1265: Identification of a predictive circulating immunological signature of response to immune checkpoint inhibitors in non-small cell lung cancer

In non-small cell lung cancer (NSCLC), response to immune checkpoint blockade (ICB) is associated with programmed cell death ligand 1 expression that is induced by interferon-γ-produced by tumor-infiltrating CD8+ T cells. However, not all tumors with a PD-L1 expression and/or CD8+ T cell infiltrate respond to ICB, and some tumors without any PD-L1 expression respond to ICB. Moreover, little is known about all the mechanisms governing ICB resistance in NSCLC. The objective of the study was to investigate a circulating immunological signature (cytokines, chemokines and immune checkpoints) which could be predictive of resistance to ICB in patients with advanced NSCLC. We performed a multiplexed analysis on 23 TruCulture® (in vitro T cells activation system) and 41 plasma samples using the Luminex® platform (Bio-Techne, MN USA). We investigated the relationship between the levels at baseline of 30 circulating analytes and the response to ICB of advanced NSCLC patients. Through the TruCulture® samples analysis, we identified two types of responders depending on T cell functionality. The responders with a functional T cell activation had lower levels of neutrophil associated analytes (CXCL5/6; p-value Citation Format: Wassila Khatir, Olivier Humbert, Jaap Neels, Léa Berland, Jonathan Benzaquen, Fabian Andrés Gallardo Rivera, Maryline Allegra, Myriam Salah, Virginie Tanga, Olivier Bordone, Julien Fayada, Virginie Lespinet-Fabre, Elodie Long-Mira, Sandra Lassalle, Patrick Brest, Valérie Vouret, Charlotte Maniel, Jacques Boutros, Simon Heeke, Véronique Hofman, Charles-Hugo Marquette, Paul Hofman, Marius Ilie. Identification of a predictive circulating immunological signature of response to immune checkpoint inhibitors in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1265.