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Review
. 2024 Oct 4:6:1409365.
doi: 10.3389/ftox.2024.1409365. eCollection 2024.

Application and interpretation of immunophenotyping data in safety and risk assessment

Victor J Johnson  1 , Michael I Luster  2 , Andrew Maier  3   4 , Corey Boles  5   6 , Eric W Miller  7 , Daniel E Arrieta  8
Affiliations
Review

Application and interpretation of immunophenotyping data in safety and risk assessment

Victor J Johnson et al. Front Toxicol. .

Abstract

The use of immunophenotyping during immunotoxicity investigations was first popularized in the 1980 s and has since become more integrated into diagnostic and non-clinical assessments. The data provided from immunophenotyping can serve as an initial source of information to guide decisions for additional, more advanced, immunotoxicity testing as well as for human health safety and risk assessment of drugs and chemicals. However, comprehensive guidance describing applications of immunophenotyping data in immunotoxicity investigations is lacking, particularly among regulatory bodies. Therefore, a critical examination is needed for the appropriate interpretations and potential misinterpretations of such data during the assessment of drug safety and chemical risk. As such, the current uses and implications of immunophenotyping data in human health safety and risk assessments has been evaluated to provide additional context for the application of current methodologies and guidelines. In addition, case studies are presented to highlight the challenges of interpreting immunophenotyping results along with incorporating the findings into immunotoxicity investigations. Based on the analyses of current approaches and methodologies, a decision flow is presented for use of immunophenotyping data during risk informed decision making.

Keywords: human health effects; immunophenotyping; immunotoxicity; risk assessment; safety.

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Conflict of interest statement

Author VJ was employed by Burleson Research Technologies, Inc. Author ML was employed by Luster Assoc. LLC. Author AM was employed by Stantec ChemRisk and Integral Consulting, Inc. Author DA was employed by Chevron Phillips Chemical Company LP. Author EM was employed by Stantec ChemRisk and Benchmark Risk Group. Author CB was emplyed by Stantec ChemRisk and Insight Exposure and Risk Sciences Group. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
General scheme used for immunophenotyping illustrating sample preparation, instrument calibration, cell analysis, gating, and data analysis by flow cytometry. Adapted from Maecker et al. (2012).
FIGURE 2
FIGURE 2
Flow diagram illustrating the decision logic for immunophenotyping data assessment described in Table 7.
See this image and copyright information in PMC

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