Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation
Background: Cases of the spontaneous regression of multiple pulmonary metastases, after radiofrequency ablation (RFA), of a single lung metastasis, have been documented to be mediated by the immune system. The interaction of immune checkpoints, e.g., PD-1/PD-L1 and CTLA-4/CD80, may explain this phen...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5738 |
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| author | James Miles Isabelle Soubeyran Florence Marliot Nicolas Pangon Antoine Italiano Carine Bellera Stephen G. Ward Franck Pagès Jean Palussière Banafshé Larijani |
| author_facet | James Miles Isabelle Soubeyran Florence Marliot Nicolas Pangon Antoine Italiano Carine Bellera Stephen G. Ward Franck Pagès Jean Palussière Banafshé Larijani |
| author_sort | James Miles |
| collection | DOAJ |
| description | Background: Cases of the spontaneous regression of multiple pulmonary metastases, after radiofrequency ablation (RFA), of a single lung metastasis, have been documented to be mediated by the immune system. The interaction of immune checkpoints, e.g., PD-1/PD-L1 and CTLA-4/CD80, may explain this phenomenon. The purpose of this study is to identify and quantify immune mechanisms triggered by RFA of pulmonary metastases originating from colorectal cancer. Methods: We used two-site time-resolved Förster resonance energy transfer as determined by frequency-domain FLIM (iFRET) for the quantification of receptor–ligand interactions. iFRET provides a method by which immune checkpoint interaction states can be quantified in a spatiotemporal manner. The same patient sections were used for assessment of ligand–receptor interaction and intratumoral T-cell labeling. Conclusion: The checkpoint interaction states quantified by iFRET did not correlate with ligand expression. We show that immune checkpoint ligand expression as a predictive biomarker may be unsuitable as it does not confirm checkpoint interactions. In pre-RFA-treated metastases, there was a significant and negative correlation between PD-1/PD-L1 interaction state and intratumoral CD3+ and CD8+ density. The negative correlation of CD8+ and interactive states of PD-1/PD-L1 can be used to assess the state of immune suppression in RFA-treated patients. |
| first_indexed | 2024-03-09T17:52:32Z |
| format | Article |
| id | doaj.art-a2889cabd37f4a10bd3cc28d4a8e44b0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:32Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a2889cabd37f4a10bd3cc28d4a8e44b02023-11-24T10:37:51ZengMDPI AGCancers2072-66942022-11-011423573810.3390/cancers14235738Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency AblationJames Miles0Isabelle Soubeyran1Florence Marliot2Nicolas Pangon3Antoine Italiano4Carine Bellera5Stephen G. Ward6Franck Pagès7Jean Palussière8Banafshé Larijani9Cell Biophysics Laboratory, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, 48940 Leioa, SpainMolecular Pathology Unit, Department of Pathology, Institut Bergonié, Cours de l’Argonne, 33076 Bordeaux, FranceImmunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, INSERM, Laboratory of Integrative Cancer Immunology, Université Paris Cité, 75006 Paris, FranceInterventional Radiology, Institut Bergonié, Cours de l’Argonne, 33076 Bordeaux, FranceEarly Phase Trials and Sarcoma, Institut Bergonié, Cours de l’Argonne, 33076 Bordeaux, FranceDepartment of Clinical and Epidemiological Research, Institut Bergonié, 33076 Bordeaux, FranceCentre for Therapeutic Innovation, Leukocyte Biology Laboratory, Life Sciences Department, University of Bath, Claverton Down, Bath BA2 7AY, UKImmunomonitoring Platform, Laboratory of Immunology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Européen Georges Pompidou, INSERM, Laboratory of Integrative Cancer Immunology, Université Paris Cité, 75006 Paris, FranceInterventional Radiology, Institut Bergonié, Cours de l’Argonne, 33076 Bordeaux, FranceCell Biophysics Laboratory, Research Centre for Experimental Marine Biology and Biotechnology (PiE) & Instituto Biofisika (UPV/EHU, CSIC), University of the Basque Country, 48940 Leioa, SpainBackground: Cases of the spontaneous regression of multiple pulmonary metastases, after radiofrequency ablation (RFA), of a single lung metastasis, have been documented to be mediated by the immune system. The interaction of immune checkpoints, e.g., PD-1/PD-L1 and CTLA-4/CD80, may explain this phenomenon. The purpose of this study is to identify and quantify immune mechanisms triggered by RFA of pulmonary metastases originating from colorectal cancer. Methods: We used two-site time-resolved Förster resonance energy transfer as determined by frequency-domain FLIM (iFRET) for the quantification of receptor–ligand interactions. iFRET provides a method by which immune checkpoint interaction states can be quantified in a spatiotemporal manner. The same patient sections were used for assessment of ligand–receptor interaction and intratumoral T-cell labeling. Conclusion: The checkpoint interaction states quantified by iFRET did not correlate with ligand expression. We show that immune checkpoint ligand expression as a predictive biomarker may be unsuitable as it does not confirm checkpoint interactions. In pre-RFA-treated metastases, there was a significant and negative correlation between PD-1/PD-L1 interaction state and intratumoral CD3+ and CD8+ density. The negative correlation of CD8+ and interactive states of PD-1/PD-L1 can be used to assess the state of immune suppression in RFA-treated patients.https://www.mdpi.com/2072-6694/14/23/5738immune checkpointsPD-1/PD-L1CTLA-4/CD80radiofrequency ablationabscopal effectFRET/FLIM |
| spellingShingle | James Miles Isabelle Soubeyran Florence Marliot Nicolas Pangon Antoine Italiano Carine Bellera Stephen G. Ward Franck Pagès Jean Palussière Banafshé Larijani Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation Cancers immune checkpoints PD-1/PD-L1 CTLA-4/CD80 radiofrequency ablation abscopal effect FRET/FLIM |
| title | Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation |
| title_full | Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation |
| title_fullStr | Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation |
| title_full_unstemmed | Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation |
| title_short | Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation |
| title_sort | determination of interactive states of immune checkpoint regulators in lung metastases after radiofrequency ablation |
| topic | immune checkpoints PD-1/PD-L1 CTLA-4/CD80 radiofrequency ablation abscopal effect FRET/FLIM |
| url | https://www.mdpi.com/2072-6694/14/23/5738 |
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