Baseline Blood CD8 + T Cell Activation Potency Discriminates Responders from Non-Responders to Immune Checkpoint Inhibition Combined with Stereotactic Radiotherapy in Non-Small-Cell Lung Cancer.

Autor: Kievit H; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Muntinghe-Wagenaar MB; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Abdulahad WH; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Rutgers A; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Hijmering-Kappelle LBM; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Hiddinga BI; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Ubbels JF; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Wijsman R; Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., van der Leij MJ; Department of Laboratory Medicine, Medical Immunology Laboratory, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Bijzet J; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Groen HJM; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Kerstjens HAM; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., van der Wekken AJ; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Kroesen BJ; Department of Laboratory Medicine, Medical Immunology Laboratory, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands., Hiltermann TJN; Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2024 Jul 19; Vol. 16 (14). Date of Electronic Publication: 2024 Jul 19.
DOI: 10.3390/cancers16142592
Abstrakt: Background: Tumor-infiltrating immune cells have been correlated with prognosis for patients treated with immune checkpoint inhibitor (ICI) treatment of various cancers. However, no robust biomarker has been described to predict treatment response yet. We hypothesized that the activation potency of circulating T cells may predict response to ICI treatment.
Methods: An exploratory analysis was conducted to investigate the association between the response to immune checkpoint inhibition (ICI) combined with stereotactic radiotherapy (SBRT) and the potency of circulating T cells to be activated. Blood-derived lymphocytes from 14 patients were stimulated ex vivo with, among others, Staphylococcal enterotoxin B (SEB) and compared to healthy controls (HCs). Patients were grouped into responders (>median progression free survival (PFS)) and non-responders (+ and CD8 + T cells in response to stimulation was measured using flow cytometry. In addition, serum levels of BAFF, IFNγ, and IL-2 receptor (sIL-2R) were measured by Luminex.
Results: At baseline, a higher percentage of activated CD8 + T cells (15.8% vs. 3.5% ( p = <0.01)) and IL-2 + CD69 + CD8 + T cells (8.8% vs. 2.9% ( p = 0.02)) was observed in responders compared to non-responders upon ex vivo stimulation with SEB. The concurrently measured serum cytokine levels were not different between responders and non-responders.
Conclusion: Baseline blood CD8 + T cell activation potency, measured by intracellular cytokine production after ex vivo stimulation, is a potential biomarker to discriminate responders from non-responders to SBRT combined with ICI.
Competing Interests: This study received funding from AstraZeneca. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. All authors declare no other competing interests.
Databáze: MEDLINE
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