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病例报告:在肿瘤免疫微环境空间结构的指导下,联合使用PD-1和酪氨酸激酶抑制剂可稳定难治性胰腺癌病情。

Case Report: Combined PD-1 and tyrosine kinase blockade stabilizes refractory pancreatic cancer guided by the spatial structure of tumor immune microenvironment.

作者信息

Yang Heqi, Ma Yuhang, Zhang Chenyan, Leng Qingqing, Cheng Ke, Zhao Chengjian, Cao Dan

机构信息

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Division of Abdominal Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Front Immunol. 2025 May 1;16:1547388. doi: 10.3389/fimmu.2025.1547388. eCollection 2025.

Abstract

Pancreatic cancer is characterized by a poor prognosis and limited responsiveness to conventional therapies, presenting a substantial therapeutic challenge. Although chemotherapy remains the cornerstone of systemic treatment, options become scarce once frontline therapies fail. While targeted therapies and immunotherapies have emerged as potential alternatives, their efficacy in pancreatic cancer is not well established. As research advances, exploring the tumor immune microenvironment (TiME) of pancreatic cancer is crucial and holds significant potential for developing novel treatment strategies.We report a case of a pancreatic cancer patient who, after the failure of frontline and second-line treatments, was treated with a pioneering combination of targeted therapy and immunotherapy to modulate the unique TiME. The targeted agent, surufatinib, is a tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor (VEGFR) 1-3, fibroblast growth factor receptor 1 (FGFR1), and colony-stimulating factor 1 receptor (CSF-1R). The immunotherapy agent, toripalimab, is an immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1). Remarkably, the patient benefitted from this regimen, exhibiting stable disease, improved clinical symptoms, and prolonged progression-free survival. This case highlights the potential of personalized therapy in treating pancreatic cancer, particularly in patients with distinctive features of the TiME that may predict favorable responses to immunotherapy. Personalized strategies that consider the spatial structure and composition of the TiME may offer a promising avenue for achieving long-term progression-free survival in patients with pancreatic cancer.

摘要

胰腺癌的特点是预后较差,对传统疗法的反应有限,这带来了巨大的治疗挑战。尽管化疗仍然是全身治疗的基石,但一旦一线治疗失败,治疗选择就会变得稀缺。虽然靶向治疗和免疫治疗已成为潜在的替代方案,但其在胰腺癌中的疗效尚未明确。随着研究的进展,探索胰腺癌的肿瘤免疫微环境(TiME)至关重要,并且在开发新的治疗策略方面具有巨大潜力。我们报告了一例胰腺癌患者,在一线和二线治疗失败后,接受了靶向治疗和免疫治疗的开创性联合治疗,以调节独特的TiME。靶向药物索凡替尼是一种酪氨酸激酶抑制剂(TKI),靶向血管内皮生长因子受体(VEGFR)1-3、成纤维细胞生长因子受体1(FGFR1)和集落刺激因子1受体(CSF-1R)。免疫治疗药物特瑞普利单抗是一种靶向程序性细胞死亡蛋白1(PD-1)的免疫检查点抑制剂。值得注意的是,该患者从该治疗方案中获益,疾病稳定,临床症状改善,无进展生存期延长。该病例突出了个性化治疗在治疗胰腺癌中的潜力,特别是对于具有TiME独特特征且可能对免疫治疗有良好反应的患者。考虑TiME的空间结构和组成的个性化策略可能为实现胰腺癌患者的长期无进展生存提供一条有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19f7/12078320/4d1349d46a04/fimmu-16-1547388-g001.jpg

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