PO.CL01.06 · 临床研究
复发性头颈部鳞状细胞癌中PD-L1、desmocollin 3与间质淋巴细胞之间的相关性
Correlation between PD-L1, desmocollin 3, and stromal lymphocytes in recurrent head and neck squamous cell carcinomas
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
引言：免疫检查点抑制剂改善了复发性/转移性头颈部癌（rmHNSCC）的结局。约20%的患者获得获益，且获益程度与PD-L1表达成正比。我们评估了PD-L1、Desmocollin-3（DSC3）与间质肿瘤浸润淋巴细胞（TIL）之间的相关性，以探索在rmHNSCC中使用DSC3特异性治疗的可能性。DSC3是在研产品CADI-05的预测性生物标志物。
方法：对rmHNSCC患者的样本采用标准方案评估PD-L1表达，并以联合阳性评分（CPS）和肿瘤阳性评分（TPS）表示。DSC3表达通过免疫组化以肿瘤阳性评分（TPS）评估，使用小鼠抗DSC3单克隆抗体（Progen，海德堡，德国，货号#61093，稀释度：1:50），在去除福尔马林固定石蜡包埋组织的石蜡后进行。TIL经苏木精和伊红染色后评估，以占总细胞的百分比表示。所有评估样本均在患者知情同意后获得。
结果：在2023年9月至2025年5月期间，共评估70份样本的PD-L1、DSC3和TIL。以CPS和TPS表示的PD-L1表达分别在77%和51%的样本中观察到。PD-L1值范围为0-95%（CPS）和0-95%（TPS）。DSC3表达在93%的样本中观察到。DSC3（TPS）值范围为0-80%。PD-L1（CPS）与DSC3表达之间未发现相关性（Spearman相关系数r = -0.1432，p = 0.3846；95%置信区间 = -0.4389至0.1805）。PD-L1（TPS）与DSC3之间存在中度负相关（r = -0.3）。所有PD-L1阴性样本均表达DSC3。PD-L1阳性和阴性样本之间的DSC3表达均值和中位值无差异。根据表达水平，TIL分为TIL≥10%和<10%的样本。TIL≥10%在40%的评估样本中观察到。所有表达PD-L1（CPS和TPS）以及DSC3的样本TIL均≥10%。5份样本中TIL缺失，且全部表达DSC3（10-40%）。
结论：DSC3在93%的rmHNSCC中表达，与PD-L1和TIL表达无关，提示DSC3特异性治疗可能有助于管理PD-L1和/或TIL缺失/低表达的rmHNSCC患者。
查看英文原文 English abstract
Introduction: Immune checkpoint inhibitors has improved outcome of recurrent /metastatic head and cancer (rmHNSCC) . Benefit is seen in around 20% pf patients and is proportionate to PD-L1 expression. We evaluated correlation between PD-L1, Desmocollin-3 (DSC3) and stromal tumor infiltrating lymphocytes (TIL) to explore possibility of using DSC3 specific therapy along rmHNSCC . DSC3 is a predictive biomarker for an investigational product CADI-05.
Methods: Samples from patients with rmHNSCC were evaluated PD-L1 expression using standard protocol and expressed as combined proportion score (CPS) and tumor proportion score ( TPS) . DSC3 expression was evaluated as tumor proportion score (TPS) by immunohistochemistry, using mouse anti-DSC3 monoclonal antibody (Progen, Heidelberg, Germany Cat#61093 dilution: 1:50) following removal of paffinization of formalin-fixed, paraffin-embedded tissue. TIL was evaluated after staining with hematoxylin and eosin and expressed as a percentage of total cells. All evaluated samples were received after informed consent of patients.
Results: Total of seventy (70) samples were evaluated between September 2023 to May 2025 for PD-L1, DSC3 and TIL. PD-L1 expression as CPS and TPS was observed in 77% and 51% of samples. PD-L1 values ranged from 0-95% ( CPS) and 0-95%(TPS). DSC3 expression was observed in 93% of samples. DSC3 (TPS) values ranged from 0-80%. No correlation was found between PD-L1(CPS) and DSC3 expression (Spearman correlation coefficient r = -0.1432, p = 0.3846; 95% Confidence interval = -0.4389 to 0.1805). There was a moderate negative correlation (r= -0.3) between PD-L1(TPS) and DSC3. All PD-L1 negative samples expressed DSC3.Mean and median DSC3 expression values were not different between PD-L1 positive and negative samples. Based on expression level TIL were grouped as samples having TIL ≥ 10% and <10%. TIL ≥ 10% were observed in 40% of evaluated samples. All samples expressing PD-L1(CPS and TPS) as well as DSC3 had TIL ≥ 10% . TIL were absent in five samples and all expressed DSC3 from 10-40%.
Conclusion: DSC3 is expressed in 93% of rmHNSCC , irrespective of PD-L1 and TIL expression suggesting DSC3 specific therapy may be useful in management of patients with rmHNSCC with absent/low PD-L1 and or TIL .
利益披露 Disclosure
V. Newaskar,
Corediagnostics Employment.
S. Sharma,
Corediagnostics Employment.
B. M. Khamar,
CADILA Pharmaceuticals Limited Employment.