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Updated: May 31, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Reduced monocytic IL10 expression in PD1 inhibitor-treated patients is a harbinger of severe immune-related adverse
Stanislav Rosnev1, Baldur Sterner1, Phillip Schiele1
1Department of Hematology, Oncology and Cancer Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health Berlin, Germany.
Background:
Despite remarkable clinical efficacy, little is known about the system-wide immunological alterations provoked by PD1 blockade. Dynamics of quantitative immune composition and functional repertoire during PD1 blockade could delineate cohort-specific patterns of treatment response and therapy-induced toxicity.
Methods:
We longitudinally assessed therapy-induced effects on the immune system in fresh whole blood using flow cytometry-based cell quantifications, accompanied by analyses of effector properties of all major immune populations upon cell-type specific stimulations. 43 cancer patients undergoing PD1 blockade were recruited with assessments performed pre-treatment and before cycles 2/4/6, which resulted in the collection of more than 30,000 cytometric data values.
Results:
We observed no intrinsic immune pattern correlating with clinical outcome before PD1 blockade initiation, but cohort-specific immune alterations emerged during therapy. The most striking evolving changes in therapy responders were an increase in activated T and NK cell subsets, which showed high IFNγ and TNFα expression upon ex vivo stimulation. Patients affected by severe immune-related adverse events (s-irAE) presented with an analogously increased number of activated CD4 + and CD8 + T cells compared to patients with no/mild irAE, but lacked the functional divergences observed between responders versus non-responders. Instead, their monocytes showed discriminatory functional deficits with less IL10 production upon stimulation, which led to an abrogated inhibition of T cell proliferation in vitro and thus may account for the observed T cell expansion in patients with s-irAE.
Conclusion:
Our holistic explorative approach allowed the delineation of clinically relevant cohorts by treatment-triggered immune changes, potentially enabling better patient stratification and further revealed new mechanistic insights into the pathogenesis of s-irAE.
