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Published on: February 8, 2018
Predicting immune checkpoint inhibitors response via fluorescence lifetime imaging microscopy: a systematic review
Carlo Cossa1, Giulio Frigato1, Massimo Lupo1
1Humanitas University, Milan, Italy.
Insights
Fluorescence Lifetime Imaging Microscopy (FLIM) shows promise in predicting immunotherapy response by quantifying molecular interactions in the tumor microenvironment, outperforming traditional methods like immunohistochemistry.
Area of Science:
- Biomedical Imaging
- Immunology
- Molecular Biology
Background:
- Traditional methods like immunohistochemistry (IHC) are insufficient for predicting immunotherapy response.
- Understanding molecular interactions within the tumor microenvironment is crucial for patient stratification.
- Immune checkpoints and their ligand interactions play a key role in treatment effectiveness.
Purpose of the Study:
- To evaluate Fluorescence Lifetime Imaging Microscopy (FLIM) as a predictive biomarker for immune checkpoint inhibitor (ICI) responsiveness.
- To review the current literature on FLIM's application in assessing the tumor and immune microenvironment in the context of ICI therapy.
Main Methods:
- Systematic literature review following PRISMA guidelines.
- Inclusion of original clinical and preclinical studies utilizing FLIM.
- Exclusion of reviews, case reports, editorials, and abstracts without full text.
Main Results:
- Molecular interaction, rather than mere expression, correlates positively with ICI treatment efficacy.
- FLIM, particularly when combined with Förster Resonance Energy Transfer (FRET), enables quantification of interactions within the tumor microenvironment.
Conclusions:
- FLIM offers a novel approach to assessing the cellular microenvironment and predicting immunotherapy outcomes.
- Further research into FLIM applications for drug interaction studies and clinical use is warranted.
Introduction:
Fluorescence Lifetime Imaging Microscopy (FLIM) is an imaging technique that allows for the visualization of the cellular microenvironment by measuring the decay time of endogenous fluorescent molecules. Its advent has allowed the acquisition of information on previously undetectable aspects of the tissue environment, which also includes some mechanisms involving immune checkpoints. Understanding the level of interaction with their ligands is of paramount importance when stratifying patients for immunotherapy, as traditional methods such as immunohistochemistry (IHC) were found to be ineffective in predicting responders.
Methods:
This review analyzes the current literature on FLIM as a means of predicting targets' responsiveness to ICIs by examining the most relevant databases. Following PRISMA guidelines, we identified the relevant literature. The predefined objective of this review was to evaluate the potential of FLIM as a predictive biomarker of responsiveness to immune checkpoint inhibitors (ICIs). Eligibility criteria included original studies (clinical or preclinical) reporting on the use of FLIM to assess tumor or immune microenvironment in the context of ICI therapy. Reviews, case reports, editorials, and abstracts without full text were excluded.
Results:
Research suggests that interaction, not expression, is positively correlated with the effectiveness of ICI treatment. FLIM, in combination with FRET, allows for the quantification of the interactions within the tumor microenvironment.
Discussion:
The scope of the review is to assist researchers in further exploring this technology for possible applications and for future drug interaction studies.
