A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer

Frontiers in Immunology

Immunology

Jose Luis Solórzano¹  Anna Vilalta-Lacarra²  Fabiola Iribarren²  María Rodríguez-Remírez³  Ander Puyalto³  Ignacio Gil-Bazo⁴  María Collantes⁵  Marga Ecay⁵  Sergio Sandiego⁶  Alejandro Francisco-Cruz⁷  Iván Peñuelas⁸  Jon Ander Simón⁹  Inés López^1,10  Daniel Ajona^1,11  Alfonso Calvo^1,11 

[1] Departamento de Anatomía Patológica y Diagnóstico Molecular, Md Anderson Cancer Center, Madrid, Spain;Unidad de Investigación Clínica de Cáncer de Pulmón Hospital Universitario 12 de octubre- Centro Nacional de Investigaciones Oncologicas (H12O-CNIO), Madrid, Spain;Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain;University of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain;Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain;University of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain;Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, Spain;University of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain;Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;Department of Oncology, Fundación Instituto Valenciano de Oncología (FIVO), Valencia, Spain;Centro de Investigación Biomédica en Red - Cáncer (CIBERONC), Madrid, Spain;Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain;Translational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, Spain;Department of Oncology, Fundación Instituto Valenciano de Oncología (FIVO), Valencia, Spain;Department of Pathology, National Institute of Cardiology Ignacio Chavez, Mexico City, Mexico;Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain;Translational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, Spain;University of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain;Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain;Translational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, Spain;University of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain;Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;University of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, Spain;Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;Centro de Investigación Biomédica en Red - Cáncer (CIBERONC), Madrid, Spain;

关键词: lung adenocarcinoma;    inhibitor of differentiation 1;    PD-1 inhibition;    immuno-PET;    pseudoprogression;   

DOI  :  10.3389/fimmu.2023.1272570

 received in 2023-08-04, accepted in 2023-09-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundHarnessing the anti-tumor immune system response by targeting the program cell death protein (PD-1) and program cell death ligand protein (PD-L1) axis has been a major breakthrough in non-small cell lung cancer (NSCLC) therapy. Nonetheless, conventional imaging tools cannot accurately assess response in immunotherapy-treated patients. Using a lung cancer syngeneic mouse model responder to immunotherapy, we aimed to demonstrate that [89Zr]-anti-PD-1 immuno-PET is a safe and feasible imaging modality to assess the response to PD-1/PD-L1 blockade in NSCLC.Materials and methodsA syngeneic mouse model responder to anti-PD-1 therapy was used. Tumor growth and response to PD-1 blockade were monitored by conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [89Zr]-labeled anti-PD-1 antibody and measured as 89Zr tumor uptake.ResultsConventional [18F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [89Zr]-anti-PD-1 uptake was substantially higher in mice that responded to PD-1 blockade. The analysis of tumor-infiltrating immune cell populations and interleukins demonstrated an increased anti-tumor effect elicited by activation of effector immune cells in PD-1-responder mice. Interestingly, a positive correlation between [89Zr]-anti-PD-1 uptake and the proportion of tumor-infiltrating lymphocytes (TILs) was found (Cor = 0.8; p = 0.001).ConclusionOur data may support the clinical implementation of immuno-PET as a promising novel imaging tool to predict and assess the response of PD-1/PD-L1 inhibitors in patients with NSCLC.

【 授权许可】

Unknown   
Copyright © 2023 Puyalto, Rodríguez-Remírez, López, Iribarren, Simón, Ecay, Collantes, Vilalta-Lacarra, Francisco-Cruz, Solórzano, Sandiego, Peñuelas, Calvo, Ajona and Gil-Bazo