論文No4049
Comprehensive serum biomarker analysis reveals IL-8 changes as the only predictor of the effectiveness of immune checkpoint inhibitors for patients with advanced non-small cell lung cancer
Hiroaki Akamatsu,Yasuhiro Koh,Makoto Nishio,...Shunichiro Iwasawa,Shintaro Nakagawa,Tetsuya Mitsudomi
LUNG CANCER, Volume 198, 108017, December 2024.
要約
この研究は、非小細胞肺がん患者に対する免疫チェックポイント阻害剤（ICI）の一種であるアテゾリズマブの治療効果を予測する新たなバイオマーカーを探索することを目的としています。研究チームは、血中の様々なタンパク質（サイトカイン、ケモカインなど）を網羅的に分析し、その変化が治療効果とどのように関連しているかを調べました。
その結果、血中のIL-8というタンパク質の減少が、アテゾリズマブ治療の効果と深く関連していることがわかりました。具体的には、治療開始前と治療中のIL-8の減少が大きい患者ほど、腫瘍が縮小する割合が高く、病気の進行が遅くなる傾向が見られました。
Take Home Message
非小細胞肺がん患者において、アテゾリズマブ治療の効果を予測する新たなバイオマーカーとして、血中のIL-8が注目されています。
治療開始前後の血中のIL-8の減少は、アテゾリズマブ治療の効果が高いことを示唆する可能性があります。
IL-8の測定は、患者一人ひとりに最適な治療法を選択する上で役立つ可能性があります。
IL-8の減少がなぜアテゾリズマブ治療の効果と関連しているのか、そのメカニズムを解明することで、より効果的ながん治療法の開発につながることが期待されます。
Objectives
Programmed cell death ligand 1 (PD-L1) expression is widely used to predict the effectiveness of PD-(L)1 inhibitors despite its imperfection. Previous studies suggested the utilization of various serum biomarkers; nonetheless, findings are inconclusive because of limited sample sizes or the focus on a single biomarker in many of these studies. This study analyzed multiplex serum biomarkers to explore their predictive ability in a large cohort of patients with advanced non-small-cell lung cancer (NSCLC) treated with a PD-L1 inhibitor in a real-world setting.
Materials and Methods
This was a sub-study of J-TAIL, a prospective observational study of atezolizumab monotherapy in pre-treated patients with advanced NSCLC. From April to October 2019, 262 patients were enrolled from 73 sites in Japan. Serum samples were collected at baseline and at the second dose of atezolizumab. Quantification of the 51 serum cytokines, chemokines, growth factors, and vascular endothelial growth factors was performed using the Luminex platform. Baseline values and fold changes of the time of the second dose to the baseline were examined in association with the effectiveness of atezolizumab.
Results
Among the 51 proteins assessed, a higher baseline interleukin (IL)-12 level, a higher soluble CD40 ligand fold change, a lower IL-8 fold change were associated with higher objective response rate (ORR). Of these, only the lower IL-8 fold change was associated with better progression-free survival (PFS) (adjusted hazard ratio, 1.98; 95 % confidence interval, 1.45–2.70; P < 0.01). Multivariate analysis demonstrated that the lower IL-8 fold change was an independent factor for both the ORR and PFS. The IL-8 fold change was independent of the neutrophil/lymphocyte ratio, and durable PFS was observed in patients with both low.
Conclusion
Comprehensive serum biomarker analysis revealed that a lower fold change in serum IL-8 was associated with better outcomes in pre-treated patients with advanced NSCLC receiving atezolizumab.