Abstract 1265: Identification of a predictive circulating immunological signature of response to immune checkpoint inhibitors in non-small cell lung cancer
Authors: Khatir Wassila , Humbert Olivier , Neels Jaap , Berland Léa , Benzaquen Jonathan , Rivera Fabian Andrés Gallardo , Allegra Maryline , Salah Myriam , Tanga Virginie , Bordone Olivier , Fayada Julien , Lespinet-Fabre Virginie , Long-Mira Elodie , Lassalle Sandra , Brest Patrick , Vouret Valérie , Maniel Charlotte , Boutros Jacques , Heeke Simon , Hofman Véronique , Marquette Charles-Hugo , Hofman Paul , Ilie Marius 
Published: June 2022

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&lt;0.05) than non-responders. They had lower levels of IL-13 and higher levers of TNFα, respectively Th2 and Th1/CD8+/NK associated analytes. All responders had lower levels of CCL17 and higher levels of CXCL10 in plasma samples, respectively M2/N2 and M1/N1 associated analytes. This study highlighted two distinct profiles of ICB responders. The first group has a functional T cell response with a favorable orientation to antitumor cytotoxic action (Th1/CD8+) and few cytokines associated with neutrophils. The second group has a poor functional T cell response, whereas their favorable response to ICB is potentially linked to the activation of the innate immune response. The plasma study highlighted the potential role of polarization of the innate response in the context of the response to ICB for all patients.

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.