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, Hanneke, Muntinghe-Wagenaar, M. Benthe, Abdulahad, Wayel H., Rutgers, Abraham, Hijmering-Kappelle, Lucie B. M., Hiddinga, Birgitta I., Ubbels, J. Fred, Wijsman, Robin, van der Leij, Marcel J., Bijzet, Johan, Groen, Harry J. M., Kerstjens, Huib A. M., van der Wekken, Anthonie J., Kroesen, Bart-Jan, Hiltermann, T. Jeroen N.
Předmět:	FLOW cytometry T cells RESEARCH funding IMMUNOTHERAPY RADIOSURGERY TUMOR markers BODY fluid examination MANN Whitney U Test DESCRIPTIVE statistics IMMUNE checkpoint inhibitors RESEARCH LUNG cancer PROGRESSION-free survival CYTOKINES COMPARATIVE studies INTERLEUKINS TUMOR necrosis factors
Zdroj:	Cancers; Jul2024, Vol. 16 Issue 14, p2592, 12p
Abstrakt:	Simple Summary: Cancer may be recognized by the immune system. For patients with non-small-cell lung cancer (NSCLC), immune checkpoint inhibitors (ICI) are a first-line treatment in most patients. However, most of these patients do not respond to ICI, implying that the treatment is ineffective, where it may have relevant side effects. Currently, there is no solid biomarker to predict response to ICI. Thus, there is an urgent need for a new biomarker to predict this response, preferably via minimally invasive techniques. We tested the potency of T cells to be activated ex vivo in the peripheral blood of patients with advanced NSCLC. We found an increased ability to activate CD8+ T cells and produce intracellular IL-2 in peripheral CD8+ T cells in patients that respond to ICI compared to non-responders and healthy controls before the start of ICI. The potency of peripheral T cells to be activated before treatment seems a promising biomarker. 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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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