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Pre-treatment polyfunctionality percentage (PFA) of CD8+ T cells is associated with development of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs).

Jonathan Thompson·Katie Palen·Smitha Menon·Hui-Zi Chen·Tyce Kearl
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Abstract

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have improved cancer survival, but immune-related adverse events (irAEs) occur frequently and can have devastating consequences. There are no validated methods to evaluate risk of irAEs prior to initiation of ICIs. MATERIALS AND METHODS: We conducted a pilot study evaluating the ability of blood-based, single-cell secretomic analysis to characterize irAEs. A total of 10 patients with thoracic malignancies who were scheduled to receive ICIs were enrolled. Each patient had a pre-ICI blood sample drawn as well as a sample at the time of irAE development or 12 weeks after ICI initiation, whichever came first. Utilizing IsoPlexis's IsoLight system, polyfunctionality percentages (PFAs) and strength indices (PSIs) were analyzed for CD4+ and CD8+ T cells. RESULTS: Five patients developed irAEs and 5 patients did not develop irAEs. Pre- and post-ICI CD8+ T cell PFA was significantly elevated in patients who developed irAEs compared with those who did not (p = 0.017 and p = 0.014, respectively). CONCLUSIONS: In this pilot study, pre-ICI CD8+ T cell PFA was associated with development of irAEs. While this is a pilot study, this is a first step toward developing a blood-based, streamlined assay to assess risk of irAEs prior to initiation of ICIs. Validation in larger cohorts is warranted.

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HumansCD8-Positive T-LymphocytesImmune Checkpoint InhibitorsFemaleMaleMiddle AgedAgedDrug-Related Side Effects and Adverse ReactionsPilot ProjectsNeoplasmsCytokinesImmunotherapyProteomicsToxicityJournal Article

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Jonathan Thompson, Katie Palen, Smitha Menon, Hui-Zi Chen, Tyce Kearl. 2026-08-19. Pre-treatment polyfunctionality percentage (PFA) of CD8+ T cells is associated with development of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs).. https://doi.org/10.1016/j.neo.2026.101353

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Journal Article resourceAged subjectCytokines subjectDrug-Related Side Effects and Adverse Reactions subjectFemale subjectHumans subjectImmune Checkpoint Inhibitors subjectImmunotherapy subjectJournal Article subjectMale subjectMiddle Aged subjectNeoplasms subjectPilot Projects subject

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