Determination of Interactive States of Immune Checkpoint Regulators in Lung Metastases after Radiofrequency Ablation

James Miles, Isabelle Soubeyran, Florence Marliot, Nicolas Pangon, Antoine Italiano, Carine Bellera, Stephen G. Ward, Franck Pagès, Jean Palussière, Banafshé Larijani

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article number5738
JournalCancers
Volume14
Issue number23
DOIs
Publication statusPublished - 31 Dec 2022

Funding

The Institutional Review Board of the Institut Bergonié (Bordeaux, France) and its ethics committee. The study was funded by the “groupe interregional de recherche Clinique et d’innovation (GIRCI)” and by Boston Scientific. Bikaintek grant for industrial doctorates in the Basque Country, the Spanish Ministry of Economy for the grants (grant number BFU 2011-28566), and the Basque Government through the BERC 3602014–2017.

Keywords

  • CTLA-4/CD80
  • FRET/FLIM
  • PD-1/PD-L1
  • abscopal effect
  • immune checkpoints
  • immune surveyance
  • radiofrequency ablation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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