Identification of a circulating immunological signature predictive of response to immune checkpoint inhibitors in patients with advanced non‐small cell lung cancer

Khatir, Wassila; Humbert, Olivier; Benzaquen, Jonathan; Bontoux, Christophe; Neels, Jaap G.; Berland, Léa; Rivera, Fabian Andrés Gallardo; Allègra, Maryline; Salah, Myriam; Tanga, Virginie; Bordone, Olivier; Fayada, Julien; Lespinet‐Fabre, Virginie; Bohly, Doriane; Long‐Mira, Elodie; Lassalle, Sandra; Vouret, Valérie; Brest, Patrick; Mograbi, Baharia; Maniel, Charlotte; Otto, Josiane; Boutros, Jacques; Heeke, Simon; Hofman, Véronique; Marquette, Charles‐Hugo; Hofman, Paul; Ilié, Marius

doi:10.1002/ctm2.1018

Cited by 5 publications

(3 citation statements)

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“…In this study, the authors used a cytometric bead array immunoassay to show that the baseline plasma levels of IL-18 and CXCL10, over the 24 cytokines selected, were correlated with the degree of tumor response. In addition, a study conducted on the same cohort we utilized revealed a correlation between elevated levels of TNFα and CXCL2 and a positive response to ICI treatment [ 23 ]. TNFα being downstream of IL-18 signaling, this result motivated us to measure IL-18.…”

Section: Discussionmentioning

confidence: 99%

Plasmatic Inactive IL-18 Predicts a Worse Overall Survival for Advanced Non-Small-Cell Lung Cancer with Early Metabolic Progression after Immunotherapy Initiation

Janho dit Hreich,

Humbert,

Pacé-Loscos

et al. 2024

Cancers

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The aim of this study was to assess the potential value of circulating active and inactive IL-18 levels in distinguishing pseudo and true tumor progression among NSCLC patients receiving immune checkpoint inhibitor treatments (ICIs). Methods: This ancillary study includes 195 patients with metastatic non-small-cell lung cancer (NSCLC) treated with ICI in monotherapy, either pembrolizumab or nivolumab. Plasmatic levels of IL-18-related compounds, comprising the inhibitor IL-18 binding protein (IL-18BP), the inactive IL-18 (corresponding to IL-18/IL-18BP complex), and the active free IL-18, were assayed by ELISA. Objective tumoral response was analyzed by 18FDG PET-CT at baseline, 7 weeks, and 3 months post treatment induction, using PERCIST criteria. Results: Plasmatic IL-18BP and total IL-18 levels are increased at baseline in NSCLC patients compared with healthy controls, whereas IL-18/IL-18BP complexes are decreased, and free IL-18 levels remain unchanged. Neither of the IL-18-related compounds allowed to discriminate ICI responding to nonresponding patients. However, inactive IL-18 levels allowed to discriminate patients with a first tumor progression, assessed after 7 weeks of treatment, with worse overall survival. In addition, we showed that neutrophil concentration is also a predictive indicator of patients’ outcomes with OS (HR = 2.6, p = 0.0001) and PFS (HR = 2.2, p = 0.001). Conclusions: Plasmatic levels of inactive IL-18, combined with circulating neutrophil concentrations, can effectively distinguish ICI nonresponding patients with better overall survival (OS), potentially guiding rapid decisions for therapeutic intensification.

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Section: Discussionmentioning

confidence: 99%

Plasmatic Inactive IL-18 Predicts a Worse Overall Survival for Advanced Non-Small-Cell Lung Cancer with Early Metabolic Progression after Immunotherapy Initiation

Janho dit Hreich,

Humbert,

Pacé-Loscos

et al. 2024

Cancers

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“…Other circulating biomarkers could be integrated into thoracic oncology as predictive factors of response to immunotherapy [ 49 , [87] , [88] , [89] ]. Thus, the analysis of the tumor mutational burden (TMB), of the repertoire of T or B lymphocyte receptors, of the level of expression of some cytokines, or of the extracellular vesicle PD-L1 dynamics are currently being studied [ 49 , 88 , 90 ]. Additionally, LB can be used to assess ctDNA clearance in advanced NSCLC patients treated with immune-chemotherapy.…”

Section: What Are the Perspectives?mentioning

confidence: 99%

Matched tissue and liquid biopsies for advanced non-small cell lung cancer patients A potentially indispensable complementary approach

Hofman¹

2023

Translational Oncology

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“…Blood was collected in EDTA tubes (Vacuette ® EDTA K2, Greiner-Bio-One, Kremsmünster, Austria) when samples could be processed <60 min after sampling or in Cell-Free DNA BCT CE-IVD tubes (Streck, La Vista, NE, USA) in cases when the samples could not be processed within this short time. Centrifugation, aliquoting, processing, and freezing at −80 • C of samples of blood products was limited to a total of 12 tubes per patient and performed at the LPCE, as previously described [23,24]…”

Section: Blood Sample Managementmentioning

confidence: 99%

The Need to Set up a Biobank Dedicated to Lymphoid Malignancies: Experience of a Single Center (Laboratory of Clinical and Experimental Pathology, University Côte d’Azur, Nice, France)

Bontoux

Marcovich

Goffinet

et al. 2023

JPM

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Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the Laboratory of Clinical and Experimental Pathology, Nice, France. We retrospectively included selected cases in a new collection at the Côte d’Azur Biobank, which contains 2150 samples from 363 cases (351 patients). The male/female ratio was 1.3, and the median age at diagnosis was 58 years. The most common lymphoma types were classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and extra-nodal marginal zone lymphoma of MALT tissue. The main sites of lymphoma were the mediastinum, lymph node, Waldeyer’s ring, and lung. The Côte d’Azur Biobank is ISO 9001 and ISO 20387 certified and aims to provide high quality and diverse biological material to support translational research projects into lymphoma. The clinico-pathological data generated by this collection should aid the development of new biomarkers to enhance the survival of patients with lymphoid malignancies.

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Identification of a circulating immunological signature predictive of response to immune checkpoint inhibitors in patients with advanced non‐small cell lung cancer

Cited by 5 publications

References 5 publications

Plasmatic Inactive IL-18 Predicts a Worse Overall Survival for Advanced Non-Small-Cell Lung Cancer with Early Metabolic Progression after Immunotherapy Initiation

Plasmatic Inactive IL-18 Predicts a Worse Overall Survival for Advanced Non-Small-Cell Lung Cancer with Early Metabolic Progression after Immunotherapy Initiation

Matched tissue and liquid biopsies for advanced non-small cell lung cancer patients A potentially indispensable complementary approach

The Need to Set up a Biobank Dedicated to Lymphoid Malignancies: Experience of a Single Center (Laboratory of Clinical and Experimental Pathology, University Côte d’Azur, Nice, France)

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