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
Department of Pulmonology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Cancers (Basel). 2024 Jul 19;16(14):2592. doi: 10.3390/cancers16142592.
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.
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 (<median PFS). The expression of the T cell activation marker CD69 and intracellular cytokines (IL-2, IFNγ, TNFα) in both CD4 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.
At baseline, a higher percentage of activated CD8 T cells (15.8% vs. 3.5% ( = <0.01)) and IL-2CD69CD8 T cells (8.8% vs. 2.9% ( = 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.
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.
肿瘤浸润免疫细胞与接受免疫检查点抑制剂（ICI）治疗的各种癌症患者的预后相关。然而，尚未有可靠的生物标志物可用于预测治疗反应。我们假设循环T细胞的激活能力可能预测对ICI治疗的反应。
进行了一项探索性分析，以研究免疫检查点抑制（ICI）联合立体定向放射治疗（SBRT）的反应与循环T细胞被激活的能力之间的关联。从14名患者采集的血液来源淋巴细胞在体外与葡萄球菌肠毒素B（SEB）等一起刺激，并与健康对照（HCs）进行比较。患者被分为反应者（>中位无进展生存期（PFS））和无反应者（<中位PFS）。使用流式细胞术测量刺激后CD4和CD8 T细胞中T细胞激活标志物CD69和细胞内细胞因子（IL-2、IFNγ、TNFα）的表达。此外，通过Luminex测量血清中BAFF、IFNγ和IL-2受体（sIL-2R）的水平。
在基线时，与无反应者相比，反应者在体外经SEB刺激后，观察到活化的CD8 T细胞百分比更高（15.8%对3.5%（P = <0.01））以及IL-2+CD69+CD8 T细胞百分比更高（8.8%对2.9%（P = 0.02））。反应者和无反应者同时测量的血清细胞因子水平没有差异。
通过体外刺激后细胞内细胞因子产生来测量的基线血液CD8 T细胞激活能力，是区分SBRT联合ICI治疗的反应者和无反应者的潜在生物标志物。
