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Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood

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Transcriptomic Determinants of Circulating Immunity Predict Immune-Related Adverse Events (irAEs) in Cancer Patients

Liting You^1,2,3,4, Jianzhao Zhai^1,2,3, Zhaodan Xin^1,2,3

¹Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Thoracic Cancer

|April 1, 2026

Summary

This study identifies five novel biomarkers in peripheral blood mononuclear cells (PBMCs) that can predict immune-related adverse events (irAEs) in cancer patients undergoing immune checkpoint inhibitor (ICI) therapy. These findings offer potential for improved patient management and targeted treatments.

Keywords:

FXYD7 circulating transcriptome immune checkpoint inhibitors immune‐related adverse events

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Area of Science:

Immunology
Oncology
Genomics

Background:

Immune checkpoint inhibitor (ICI) therapy has shown success in treating solid tumors.
Immune-related adverse events (irAEs) present significant challenges in managing ICI therapy.
Reliable biomarkers for predicting irAEs are currently limited.

Purpose of the Study:

To identify novel biomarkers in peripheral blood mononuclear cells (PBMCs) for predicting irAEs in cancer patients receiving ICI therapy.
To validate the predictive capability of identified biomarkers for irAEs.
To inform precise management and targeted treatment strategies for irAEs.

Main Methods:

Whole transcriptomic RNA sequencing of PBMCs from cancer patients treated with PD-1/PD-L1 blockade.
Validation of candidate biomarkers using RT-PCR.
IrAEs-free survival analysis and subgroup analysis.
Development of LASSO regression prediction classifiers.

Main Results:

Transcriptomic profiles of PBMCs differentiated irAEs patients from non-irAEs patients.
Five candidate biomarkers identified: FXYD7, SPSB2, SLC35E2A, C2, and SERPING1.
Biomarker expression levels correlated with irAEs-free survival and severity.
Prediction classifiers achieved high accuracy (AUC=0.91 for all grades, AUC=0.94 for severe irAEs).

Conclusions:

Circulating immunological determinants in PBMCs are crucial for irAEs.
Identified biomarkers show promise for predicting irAEs in ICI-treated cancer patients.
These biomarkers can guide future precise management and targeted treatment strategies for irAEs.