揭示肿瘤 cGAS 表达在预测非小细胞肺癌患者对 PD-1/L1 抑制剂反应中的作用。

IF 4.6 2区 医学 Q2 IMMUNOLOGY Cancer Immunology, Immunotherapy Pub Date : 2024-11-02 DOI:10.1007/s00262-024-03861-9
Yuichi Ozawa, Yasuhiro Koh, Ryota Shibaki, Yuhei Harutani, Hiroaki Akamatsu, Atsushi Hayata, Takeya Sugimoto, Yuka Kitamura, Junya Fukuoka, Masanori Nakanishi, Nobuyuki Yamamoto
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引用次数: 0

摘要

目的:cGAS/STING肿瘤表达对PD-1/L1抑制剂疗效和肿瘤微环境的影响仍有待阐明:cGAS/STING肿瘤表达对PD-1/L1抑制剂疗效和肿瘤微环境的影响仍有待阐明:在2015年12月至2018年9月对106例接受PD-1/L1抑制剂治疗的晚期NSCLC患者进行的一项前瞻性生物标志物研究的事后分析中,分析了68例患者治疗前的肿瘤组织,使用免疫组化染色和H-评分测量了cGAS和STING的表达。此外,还对治疗开始前和治疗开始后4-6周的40种血清蛋白进行了量化:结果:cGAS和STING H评分的中位数分别为220(范围为5-300)和190(范围为0-300)。结论:在PD-L1较高的NSCLC中,cGAS表达(而非STING)可预测PD-1/L1抑制剂疗效不佳,这可能是由于TGF-β介导的免疫抑制环境所致 (UMIN000024414)。
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Uncovering the role of tumor cGAS expression in predicting response to PD-1/L1 inhibitors in non-small cell lung cancer.

Objectives: The impact of cGAS/STING tumor expression on PD-1/L1 inhibitor efficacy and the tumor microenvironment remain to be elucidated.

Methods: In a post-hoc analysis of a prospective biomarker study with 106 advanced NSCLC patients treated with PD-1/L1 inhibitors from December 2015 to September 2018, tumor tissue before treatment from 68 patients was analyzed. cGAS and STING expression were measured using immunohistochemical staining and H-scores. Additionally, 40 serum proteins were quantified before and 4-6 weeks after treatment initiation.

Results: Median cGAS and STING H-scores were 220 (range, 5-300) and 190 (range, 0-300), respectively. There were no differences in cGAS or STING H-scores between the high (tumor proportion score [TPS] ≥ 50) and low (TPS < 50) PD-L1groups (p = 0.990 and 0.283, respectively). Unexpectedly, patients with high cGAS (H-score ≥ 220) demonstrated significantly shorter progression-free survival (PFS) of PD-1/L1 inhibitors when the PD-L1 TPS was high (median PFS: 143 days vs. not reached; p = 0.028); PFS at 18 months was 7% and 53% in the high and low cGAS groups, respectively while STING expression did not impact PFS. In serum protein analyses, high cGAS H-score was associated with significantly higher TGF-β1 and TGF-β2 before PD-1/L1 inhibition (47.5 vs. 22.3 ng/l, p = 0.023; 2118 vs. 882 pg/ml, p = 0.037); additionally, the cGAS H-score significantly correlated with TGF-β1 (r = 0.451, p = 0.009) and TGF-β2 (r = 0.375, p = 0.031) basal levels.

Conclusion: cGAS expression, but not STING, predicts poor PD-1/L1 inhibitor efficacy in NSCLC with high PD-L1, potentially due to a TGF-β-mediated immunosuppressive environment (UMIN000024414).

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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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