Zou Yunzhi, Duan Hao, Deng Zekun, Xiang Rong, Zhao Jixiang, Zhang Zhenhua, Hu Wanming, Yang Yuanzhong, Yan Zeming, Wen Shujuan, Liu Zexian, Zhang Gao, Mou Yonggao, Li Depei, Jiang Xiaobing
Department of Neurosurgery/Neuro-oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Mol Cell Biochem. 2025 Apr;480(4):2377-2400. doi: 10.1007/s11010-024-05064-3. Epub 2024 Aug 1.
Brain metastasis (BM) in laryngeal squamous cell carcinoma (LSCC) is uncommon but prognosis is poor. Anti-PD-1 immunotherapy benefits some advanced LSCC cases, yet its efficiency is limited by tumor complexity. We analyzed paired metastatic tumor samples from before and after immunotherapy using single-cell RNA sequencing (scRNA-seq), along with a primary LSCC dataset and bulk RNA sequencing. This identified changes post-immunotherapy and revealed differences in single-cell transcriptomes among LSCC, primBM, and neoBM. Our findings show that anti-PD-1 treatment suppresses metastasis-promoting pathways like VEGF and EMT in cancer cells, and alters immune cell functions. Notably, it upregulates T cell activation, leading to CD8 T cell exhaustion from excess heat shock proteins, notably HSPA8. However, CD8 T cell cytotoxic functions improve post-treatment. In myeloid cells, anti-PD-1 therapy enhances antigen presentation and promotes a proinflammatory shift post-metastasis. Additionally, NUPR1 is linked to BM in LSCC, and NEAT1 is a potential metastatic cancer cell cycle participant. Our study provides insights into cancer heterogeneity and the impact of PD-1 immunotherapy on metastasis, aiding precise diagnosis and prognosis.
喉鳞状细胞癌（LSCC）中的脑转移（BM）并不常见，但预后较差。抗PD-1免疫疗法对一些晚期LSCC病例有益，但其疗效受到肿瘤复杂性的限制。我们使用单细胞RNA测序（scRNA-seq）分析了免疫治疗前后配对的转移瘤样本，以及一个原发性LSCC数据集和批量RNA测序。这确定了免疫治疗后的变化，并揭示了LSCC、原发性脑转移瘤（primBM）和新生脑转移瘤（neoBM）之间单细胞转录组的差异。我们的研究结果表明，抗PD-1治疗可抑制癌细胞中促进转移的途径，如VEGF和EMT，并改变免疫细胞功能。值得注意的是，它上调T细胞活化，导致CD8 T细胞因过量热休克蛋白（尤其是HSPA8）而耗竭。然而，CD8 T细胞的细胞毒性功能在治疗后有所改善。在髓样细胞中，抗PD-1治疗增强抗原呈递，并促进转移后的促炎转变。此外，NUPR1与LSCC中的脑转移有关，而NEAT1是转移性癌细胞周期的潜在参与者。我们的研究为癌症异质性以及PD-1免疫疗法对转移的影响提供了见解，有助于精确诊断和预后。
