A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer
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 asse...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272570/full |
| _version_ | 1797671333518114816 |
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| author | Ander Puyalto Ander Puyalto Ander Puyalto María Rodríguez-Remírez María Rodríguez-Remírez María Rodríguez-Remírez Inés López Inés López Fabiola Iribarren Fabiola Iribarren Jon Ander Simón Jon Ander Simón Jon Ander Simón Marga Ecay Marga Ecay María Collantes María Collantes Anna Vilalta-Lacarra Anna Vilalta-Lacarra Alejandro Francisco-Cruz Jose Luis Solórzano Jose Luis Solórzano Sergio Sandiego Iván Peñuelas Iván Peñuelas Iván Peñuelas Alfonso Calvo Alfonso Calvo Alfonso Calvo Daniel Ajona Daniel Ajona Daniel Ajona Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo |
| author_facet | Ander Puyalto Ander Puyalto Ander Puyalto María Rodríguez-Remírez María Rodríguez-Remírez María Rodríguez-Remírez Inés López Inés López Fabiola Iribarren Fabiola Iribarren Jon Ander Simón Jon Ander Simón Jon Ander Simón Marga Ecay Marga Ecay María Collantes María Collantes Anna Vilalta-Lacarra Anna Vilalta-Lacarra Alejandro Francisco-Cruz Jose Luis Solórzano Jose Luis Solórzano Sergio Sandiego Iván Peñuelas Iván Peñuelas Iván Peñuelas Alfonso Calvo Alfonso Calvo Alfonso Calvo Daniel Ajona Daniel Ajona Daniel Ajona Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo |
| author_sort | Ander Puyalto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T21:13:49Z |
| format | Article |
| id | doaj.art-6925a7c87bd849e1b214135adddcbb6a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T21:13:49Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6925a7c87bd849e1b214135adddcbb6a2023-09-29T05:35:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12725701272570A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancerAnder Puyalto0Ander Puyalto1Ander Puyalto2María Rodríguez-Remírez3María Rodríguez-Remírez4María Rodríguez-Remírez5Inés López6Inés López7Fabiola Iribarren8Fabiola Iribarren9Jon Ander Simón10Jon Ander Simón11Jon Ander Simón12Marga Ecay13Marga Ecay14María Collantes15María Collantes16Anna Vilalta-Lacarra17Anna Vilalta-Lacarra18Alejandro Francisco-Cruz19Jose Luis Solórzano20Jose Luis Solórzano21Sergio Sandiego22Iván Peñuelas23Iván Peñuelas24Iván Peñuelas25Alfonso Calvo26Alfonso Calvo27Alfonso Calvo28Daniel Ajona29Daniel Ajona30Daniel Ajona31Ignacio Gil-Bazo32Ignacio Gil-Bazo33Ignacio Gil-Bazo34Ignacio Gil-Bazo35Ignacio Gil-Bazo36Department of Medical Oncology, Clínica Universidad de Navarra, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDepartment of Medical Oncology, Clínica Universidad de Navarra, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDepartment of Medical Oncology, Clínica Universidad de Navarra, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainDepartment of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, SpainTranslational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, SpainTranslational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, SpainTranslational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, SpainDepartment of Medical Oncology, Clínica Universidad de Navarra, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainDepartment of Pathology, National Institute of Cardiology Ignacio Chavez, Mexico City, MexicoDepartamento de Anatomía Patológica y Diagnóstico Molecular, Md Anderson Cancer Center, Madrid, SpainUnidad de Investigación Clínica de Cáncer de Pulmón Hospital Universitario 12 de octubre- Centro Nacional de Investigaciones Oncologicas (H12O-CNIO), Madrid, SpainDepartment of Oncology, Fundación Instituto Valenciano de Oncología (FIVO), Valencia, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDepartment of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, SpainTranslational Molecular Imaging Unit, Clínica Universidad de Navarra, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain0Centro de Investigación Biomédica en Red - Cáncer (CIBERONC), Madrid, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain0Centro de Investigación Biomédica en Red - Cáncer (CIBERONC), Madrid, SpainDepartment of Medical Oncology, Clínica Universidad de Navarra, Pamplona, SpainUniversity of Navarra, Cima-University of Navarra, Program in Solid Tumors, Pamplona, SpainInstituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, SpainDepartment of Oncology, Fundación Instituto Valenciano de Oncología (FIVO), Valencia, Spain0Centro de Investigación Biomédica en Red - Cáncer (CIBERONC), Madrid, SpainBackgroundHarnessing 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272570/fulllung adenocarcinomainhibitor of differentiation 1PD-1 inhibitionimmuno-PETpseudoprogression |
| spellingShingle | Ander Puyalto Ander Puyalto Ander Puyalto María Rodríguez-Remírez María Rodríguez-Remírez María Rodríguez-Remírez Inés López Inés López Fabiola Iribarren Fabiola Iribarren Jon Ander Simón Jon Ander Simón Jon Ander Simón Marga Ecay Marga Ecay María Collantes María Collantes Anna Vilalta-Lacarra Anna Vilalta-Lacarra Alejandro Francisco-Cruz Jose Luis Solórzano Jose Luis Solórzano Sergio Sandiego Iván Peñuelas Iván Peñuelas Iván Peñuelas Alfonso Calvo Alfonso Calvo Alfonso Calvo Daniel Ajona Daniel Ajona Daniel Ajona Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo Ignacio Gil-Bazo A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer Frontiers in Immunology lung adenocarcinoma inhibitor of differentiation 1 PD-1 inhibition immuno-PET pseudoprogression |
| title | A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer |
| title_full | A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer |
| title_fullStr | A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer |
| title_full_unstemmed | A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer |
| title_short | A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer |
| title_sort | novel 89zr anti pd 1 pet ct to assess response to pd 1 pd l1 blockade in lung cancer |
| topic | lung adenocarcinoma inhibitor of differentiation 1 PD-1 inhibition immuno-PET pseudoprogression |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1272570/full |
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