PD-L1 与 CD44 表达和患者生存的显着关联:胰腺癌中免疫治疗和癌症干细胞下调的途径。
Significant Association of PD-L1 With CD44 Expression and Patient Survival: Avenues for Immunotherapy and Cancer Stem Cells Downregulation in Pancreatic Cancers.
发表日期:2024
作者:
Saleema Mehboob Ali, Yumna Adnan, Zubair Ahmad, Tabish Chawla, S M Adnan Ali
来源:
Stem Cell Research & Therapy
摘要:
背景:胰腺癌以其侵袭性而闻名。这种侵袭性可能归因于癌症干细胞(CSC)的存在,它会促进复发、转移和对化疗的抵抗。靶向 CSC 对于扭转胰腺恶性肿瘤的这种侵袭性至关重要。文献强调了 PD-L1 表达与各种癌症中 CSC 的关联,表明免疫疗法是一种有前途的治疗方法。本研究旨在通过检查免疫疗法与选定的 CSC 标志物表达的关联来研究免疫疗法在胰腺癌中的潜力。方法:对2015年1月至2022年10月在阿迦汗大学医院确诊的56例胰腺癌患者进行回顾性队列研究。排除后,基于拒绝提供同意书或随访数据不完整,纳入38例患者。研究。对福尔马林固定石蜡包埋 (FFPE) 肿瘤组织样本进行免疫组织化学,以评估 CSC 标记物(CD133、CD44 和 L1CAM)和免疫检查点抑制剂标记物 (PD-L1) 的表达。采用统计分析来确定标志物表达、临床因素和总生存率之间的关联。结果:研究显示,86.8%的胰腺癌病例表现出PD-L1阳性表达。此外,观察到 PD-L1 表达与 CD44 蛋白的存在 (p = 0.030) 以及患者的总生存期 (p = 0.023) 存在显着相关性。结论:我们的研究结果表明 PD-L1 与 CD44 标志物表达以及患者生存率显着相关。这项研究表明有可能成为研究免疫疗法在减少胰腺癌中表达 CD44 的 CSC 方面的功效的基础,从而有可能改善患者的治疗效果。版权所有 © 2024 Saleema Mehboob Ali 等人。
Background: Pancreatic cancers are known for their aggressive nature. This aggressiveness may be attributed to the presence of cancer stem cells (CSCs), which promote relapse, metastasis, and resistance to chemotherapy. Targeting CSCs is essential to reverse this aggressiveness in pancreatic malignancies. Literature highlights the association of PD-L1 expression with CSCs in various cancers, suggesting immunotherapy as a promising therapeutic approach. This study is aimed at investigating the potential of immunotherapy in pancreatic cancers by examining its association with selected CSC marker expression. Method: A retrospective cohort study was conducted involving 56 patients with confirmed diagnoses of pancreatic cancers at Aga Khan University Hospital from January 2015 to October 2022. After exclusions, based on refusal to provide consent or incomplete follow-up data, 38 patients were enrolled in the study. Immunohistochemistry was performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue samples to assess the expression of CSC markers (CD133, CD44, and L1CAM) and immune checkpoint inhibitor marker (PD-L1). Statistical analysis was employed to determine associations between marker expression, clinical factors, and overall survival. Results: The study revealed that 86.8% of pancreatic cancer cases exhibited positive PD-L1 expression. Moreover, a significant association of PD-L1 expression was observed with the presence of CD44 protein (p = 0.030), as well as with the overall survival of patients (p = 0.023). Conclusion: Our findings show a significant association of PD-L1 with CD44 marker expression as well as patient survival. This research shows the potential to serve as the foundation for investigating the efficacy of immunotherapy in reducing CD44-expressing CSCs in pancreatic cancer, potentially enhancing patient outcomes.Copyright © 2024 Saleema Mehboob Ali et al.