University Skin Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
J Eur Acad Dermatol Venereol. 2024 Oct;38(10):2017-2023. doi: 10.1111/jdv.20177. Epub 2024 Jun 15.
Adjuvant treatment of stage II-IV melanoma with PD-1-based immune checkpoint inhibitors (ICI) has improved relapse-free survival (RFS) and has therefore become a standard-of-care treatment option. Approximately 25%-30% of patients still recur within 1 year. Predictive biomarkers reflecting real-world data are desired. The predictive relevance of tumour tissue PD-L1 expression in the adjuvant setting remains inconclusive.
This retrospective, observational study was conducted to evaluate the value of PD-L1 expression scores in different tumour tissue locations in predicting response towards adjuvant immunotherapeutic treatment.
Tumour tissue taken prior to anti-PD-1 adjuvant ICI in 243 stage II-IV melanoma patients was collected at University Skin Cancer Center Hamburg. PD-L1 expression was evaluated on immune cells (ICS), tumour cells (TPS) and combined (CPS). Scores were determined by independent pathological physician quantification and correlated with therapy outcome at different cut-off (CO) levels (relapse-free survival, RFS) for different tumour tissue locations (primary tumour, metastases).
A total of 104 patients were eligible for analysis. Positivity of ICS, TPS and CPS showed no predictive RFS outcome association at different CO levels when analysed irrespective of tissue origin. In primary tumours, ICS at CO 1% showed a significantly improved RFS upon positivity (HR 0.22). In contrast, positivity to TPS (CO 1%) correlated significantly and independently with improved RFS when evaluated in metastatic tumour tissue specimens (HR 0.37).
PD-L1 tumour tissue expression may serve as a predictive biomarker for adjuvant ICI treatment response stratification in melanoma, but caution should be spent on the origin of tumour tissue analysed. The cell-type relevant for the predictive value of PD-L1 expression is tissue-specific with immune cells being important in primary tumours while tumour cells are key in metastases. The present results should be validated in a multicentre cohort.
基于 PD-1 的免疫检查点抑制剂（ICI）辅助治疗 II-IV 期黑色素瘤改善了无复发生存（RFS），因此成为一种标准的治疗选择。大约 25%-30%的患者在 1 年内仍会复发。人们希望有反映真实世界数据的预测性生物标志物。在辅助治疗环境下，肿瘤组织 PD-L1 表达的预测相关性仍不确定。
本回顾性观察性研究旨在评估不同肿瘤组织位置的 PD-L1 表达评分在预测辅助免疫治疗反应方面的价值。
在汉堡大学皮肤癌中心，采集了 243 例 II-IV 期黑色素瘤患者在接受抗 PD-1 辅助 ICI 治疗前的肿瘤组织。评估了免疫细胞（ICS）、肿瘤细胞（TPS）和联合（CPS）的 PD-L1 表达。评分由独立病理医生定量，并与不同肿瘤组织位置（原发肿瘤、转移瘤）的不同截断（CO）水平（无复发生存，RFS）的治疗结果相关。
共有 104 例患者符合分析条件。当无论组织来源如何分析时，不同 CO 水平的 ICS、TPS 和 CPS 的阳性率与 RFS 无预测结果关联。在原发肿瘤中，当 CO 为 1%时，ICS 阳性与 RFS 显著改善相关（HR 0.22）。相反，当在转移性肿瘤组织标本中评估时，TPS 阳性（CO 为 1%）与 RFS 显著相关且独立相关（HR 0.37）。
PD-L1 肿瘤组织表达可作为黑色素瘤辅助 ICI 治疗反应分层的预测性生物标志物，但应注意分析的肿瘤组织来源。对 PD-L1 表达预测价值有影响的细胞类型具有组织特异性，免疫细胞在原发肿瘤中很重要，而肿瘤细胞在转移瘤中是关键。本研究结果应在多中心队列中进行验证。
