PD-L1 and Notch as novel biomarkers in pancreatic sarcomatoid carcinoma: a pilot study

The improved immunological understanding revealed the tumor microenvironment as an appealing driver to restore the immune response against cancer cells resulting in a paradigm shift in the oncology field. However, the complexity of the tumor milieu suggests the role of several pathways linking in immunomodulation mechanisms. Pancreatic cancer represents a model of the intricate relationship between malignant cells and their surrounding neighborhood.
In this study, we analyzed, retrospectively, six cases of rare pancreatic sarcomatoid carcinoma (PSC) and evaluated the expression of PD-L1 and Notch, aiming to explore new attributes in immunophenotype.
PD-L1 CPS ≥ 1was common in PSCs (83%) with half samples expressing PD-L1 CPS ≥ 50. Notch1 and Notch3 demonstrated a high range of expression. A direct significant correlation between PD-L1 and Notch3 overexpression (r = 0.7; p = 0.036) has been observed. Immunofluorescence studies revealed a co-localization of Notch3 and PD-L1 when both proteins were over-expressed within cytoplasmic or membranous compartments of the same cells.
Our data identify a unique biological characterization of this rare pancreatic histotype. These findings provide a rationale for future studies evaluating the potential crosstalk between PD-L1/PD-1 axis and Notch pathways and prompting the development of novel therapeutics strategy.

随着免疫学认知的不断深化，肿瘤微环境（tumor microenvironment, TME）被证实是重塑抗肿瘤免疫应答的关键驱动因子，这一发现推动了肿瘤学领域的范式革新。然而，肿瘤微环境的复杂性表明，多条通路共同参与免疫调节机制。胰腺癌可作为研究恶性细胞与其周围微环境间复杂相互作用的经典模型。
本研究回顾性分析了6例罕见的胰腺肉瘤样癌（pancreatic sarcomatoid carcinoma, PSC）病例，检测了PD-L1（Programmed Death-Ligand 1）与Notch的表达水平，旨在探索该肿瘤免疫表型的新特征。
PD-L1联合阳性评分（Combined Positive Score, CPS）≥1在PSC病例中较为常见（占比83%），其中半数样本的CPS≥50。Notch1与Notch3均呈现出较高的表达水平。研究发现，PD-L1与Notch3过表达之间存在显著的直接相关性（相关系数r=0.7，P=0.036）。免疫荧光实验结果显示，当两种蛋白在同一细胞的胞质或细胞膜区域过表达时，Notch3与PD-L1存在共定位现象。
本研究明确了这种罕见胰腺组织学亚型的独特生物学特征。上述研究结果为后续探索PD-L1/PD-1（Programmed Death Receptor 1, PD-1）轴与Notch通路间的潜在串扰提供了理论依据，同时也为新型治疗策略的开发指明了方向。