Muto Satoshi, Ozaki Yuki, Yamaguchi Hikaru, Watanabe Masayuki, Okabe Naoyuki, Matsumura Yuki, Hamada Kazuyuki, Suzuki Hiroyuki
Department of Chest Surgery, Fukushima Medical University, Fukushima, Japan.
Cancer Diagn Progn. 2025 Jan 3;5(1):32-41. doi: 10.21873/cdp.10409. eCollection 2025 Jan-Feb.
BACKGROUND/AIM: Tumor intrinsic β-catenin signaling has been reported to influence the tumor immune microenvironment and may be a resistance mechanism to immune checkpoint inhibitors in various cancers.
We studied the association between tumor β-catenin expression and survival in 50 patients with non-small cell lung cancer (NSCLC) treated with anti-programmed death-1 antibody monotherapy. Tumor β-catenin expression was evaluated by immunohistochemistry.
Patients with positive tumor β-catenin expression (20% of all patients) had worse progression-free survival and overall survival compared with those with negative tumor β-catenin expression. Patients with positive tumor β-catenin expression had reduced CD8 cell and CD11c cell infiltration into tumor nests than those with negative tumor β-catenin expression. RT-PCR of tumor tissue revealed that patients with positive tumor β-catenin expression showed lower gene expression of CD8A, CD4, IFN-γ, BATF3, and CCL4. Knockdown of CTNNB1 tended to increase CCL4 expression, likely mediated by ATF3, in a lung cancer cell line with positive β-catenin expression.
NSCLC patients with positive tumor β-catenin expression that were treated with anti-programmed death-1 antibody monotherapy had poor prognosis.
背景/目的：据报道，肿瘤内在的β-连环蛋白信号传导会影响肿瘤免疫微环境，并且可能是多种癌症中免疫检查点抑制剂的耐药机制。
我们研究了50例接受抗程序性死亡-1抗体单药治疗的非小细胞肺癌（NSCLC）患者的肿瘤β-连环蛋白表达与生存之间的关联。通过免疫组织化学评估肿瘤β-连环蛋白表达。
肿瘤β-连环蛋白表达阳性的患者（占所有患者的20%）与肿瘤β-连环蛋白表达阴性的患者相比，无进展生存期和总生存期更差。肿瘤β-连环蛋白表达阳性的患者与肿瘤β-连环蛋白表达阴性的患者相比，肿瘤巢内CD8细胞和CD11c细胞浸润减少。肿瘤组织的逆转录-聚合酶链反应（RT-PCR）显示，肿瘤β-连环蛋白表达阳性的患者CD8A、CD4、IFN-γ、BATF3和CCL4的基因表达较低。在β-连环蛋白表达阳性的肺癌细胞系中，CTNNB1的敲低倾向于增加CCL4表达，这可能由ATF3介导。
接受抗程序性死亡-1抗体单药治疗的肿瘤β-连环蛋白表达阳性的NSCLC患者预后较差。
