Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Fresh-blood immune profiling of immune-related adverse events in real-world patients identifies organ-specific and steroid responsiveness signatures.

Abstract

Background: Immune checkpoint inhibition (ICI) provides durable benefit across several cancers but carries a substantial risk of immune-related adverse events (irAEs). Management relies primarily on corticosteroids, yet responses are variable and difficult to predict. In this observational study, we explored whether early immune phenotypes in fresh whole blood reflect organ-specific irAEs and corticosteroid responsiveness. Materials and methods: We prospectively enrolled patients receiving ICI who developed grade 2-4 colitis, hepatitis, or nephritis. Peripheral blood was collected at irAE onset (T0) and during early management (T1). Immune profiling was carried out on fresh blood by flow cytometry and unsupervised clustering. Results: Twenty-seven patients were included (colitis n = 13, hepatitis n = 11, nephritis n = 3). Organ-specific immune patterns were observed at irAE onset: hepatitis showed higher CD27+ T cells and naive B cells; nephritis exhibited reduced T cells and expansion of CD16- natural killer cells; and colitis displayed a more variable profile. Patients were categorized as corticosteroid responders (n = 8), refractory (n = 9), or relapse (n = 10). At T0, responders showed more CD38+ T cells and naive B cells with fewer classical monocytes, relapse patients had increased memory B cells, and refractory patients had lower CD27+ T cells and elevated classical monocytes. Immune shifts from T0 to T1 were modest, though fold-change analyses revealed response-associated patterns, such as preserved CD56+ T cells and monocyte expansion in responders. Conclusions: In this explorative study, fresh-blood immunophenotyping suggested associations between irAE type, early immune signatures, and corticosteroid response. These hypothesis-generating and preliminary findings support further research into a more individualized immune-guided approach to irAE management.