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

Hanneke Kievit ¹, M Benthe Muntinghe-Wagenaar ¹, Wayel H Abdulahad ²

⁰Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.

Cancers +

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July 27, 2024

View abstract on PubMed

Summary

Baseline CD8+ T cell activation potency may predict response to immune checkpoint inhibitor (ICI) and stereotactic radiotherapy (SBRT) treatment. Higher T cell activation in blood samples correlated with better outcomes in cancer patients receiving ICI therapy.

Area Of Science

Immunology
Oncology
Biomarker Discovery

Background

Tumor-infiltrating immune cells are linked to prognosis in cancer patients receiving immune checkpoint inhibitor (ICI) therapy.
A reliable biomarker to predict ICI treatment response is currently lacking.
This study investigates circulating T cell activation potency as a potential predictive biomarker.

Purpose Of The Study

To explore the association between circulating T cell activation potency and response to immune checkpoint inhibition (ICI) combined with stereotactic radiotherapy (SBRT).
To identify potential biomarkers for predicting treatment efficacy in cancer patients.

Main Methods

An exploratory analysis involving 14 cancer patients undergoing ICI and SBRT.
Ex vivo stimulation of blood lymphocytes with Staphylococcal enterotoxin B (SEB).
Flow cytometry to measure T cell activation markers (CD69) and intracellular cytokines (IL-2, IFNγ, TNFα) in CD4+ and CD8+ T cells.
Serum cytokine level measurements (BAFF, IFNγ, sIL-2R) using Luminex.

Main Results

Responders showed a significantly higher percentage of activated CD8+ T cells (15.8% vs. 3.5%) and IL-2+CD69+CD8+ T cells (8.8% vs. 2.9%) upon ex vivo SEB stimulation compared to non-responders.
No significant differences in serum cytokine levels were observed between responders and non-responders.
Higher baseline CD8+ T cell activation potency was associated with better progression-free survival (PFS).

Conclusions

Baseline circulating CD8+ T cell activation potency, assessed via intracellular cytokine production after ex vivo stimulation, shows promise as a predictive biomarker.
This biomarker can potentially discriminate between responders and non-responders to SBRT combined with ICI therapy.
Further validation is warranted to establish this as a robust clinical tool.

Keywords:

NSCLC T cell function assay biomarker cytokines immune checkpoint inhibition immunotherapy liquid biopsy