基于PD-1的免疫检查点抑制（ICI）是当前黑色素瘤治疗的主要支柱。肿瘤PD-L1表达是少数预测ICI治疗结果的生物标志物之一。本研究的目标是系统地调查肿瘤组织类型对PD-L1表达与ICI治疗结果相关性的影响。从2014年2月至2020年5月，在前瞻性DeCOG队列研究ADOREG/TRIM（CA209-578; NCT05750511）中，收集了来自448名接受PD-1-based ICI治疗的不可切除转移性黑色素瘤患者的术前肿瘤组织。主要研究终点是最佳总体反应（BOR），次要终点是无进展生存期（PFS）和总生存期（OS）。所有终点均与肿瘤PD-L1表达（用clone 28-8定量化；截断值≥5%）相关，并按组织类型分层。肿瘤PD-L1在95个原发肿瘤（PT；阳性率36.8%）、153个皮肤/皮下（阳性率34.0%）、115个淋巴结（LN；阳性率50.4%）和85个器官（阳性率40.8%）转移中进行了测定。如果确定在LN中（OR = 0.319；95% CI = 0.138-0.762；P = 0.010），肿瘤PD-L1与BOR相关，但在皮肤/皮下转移中没有相关性（OR = 0.656；95% CI = 0.311-1.341；P = 0.26）。在LN转移中确定的PD-L1阳性与良好的生存有关（PFS，HR = 0.490；95% CI = 0.310-0.775；P = 0.002；OS，HR = 0.519；95% CI = 0.307-0.880；P = 0.014）。在PT确定的PD-L1阳性与生存相关性较小（PFS，HR = 0.757；95% CI = 0.467-1.226；P = 0.27；OS；HR = 0.528；95% CI = 0.305-0.913；P = 0.032）。在皮肤/皮下转移中确定的PD-L1没有相关的生存差异（PFS，HR = 0.825；95% CI = 0.555-1.226；P = 0.35；OS，HR = 1.083；95% CI = 0.698-1.681；P = 0.72）。对于黑素瘤的PD-1-based免疫疗法，与治疗结果相关性较强的是在LN转移中确定的肿瘤PD-L1，而在PT或器官转移中确定的PD-L1相关性较小。在皮肤/皮下转移中确定的PD-L1没有相关性，因此在临床决策中应谨慎使用。 Bristol-Myers Squibb（ADOREG/TRIM，NCT05750511）；德国研究基金会（DFG；临床科学家计划UMEA）；Else Kröner-Fresenius-Stiftung（EKFS；医学科学家学院UMESciA）。版权所有©2023作者。由Elsevier B.V.出版。保留所有权利。

PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one of few biomarkers predicting ICI therapy outcome. The objective of the present study was to systematically investigate whether the type of tumor tissue examined for PD-L1 expression has an impact on the correlation with ICI therapy outcome.Pre-treatment tumor tissue was collected within the prospective DeCOG cohort study ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received PD-1-based ICI for non-resectable metastatic melanoma. The primary study endpoint was best overall response (BOR), secondary endpoints were progression-free (PFS) and overall survival (OS). All endpoints were correlated with tumor PD-L1 expression (quantified with clone 28-8; cutoff ≥5%) and stratified by tissue type.Tumor PD-L1 was determined in 95 primary tumors (PT; 36.8% positivity), 153 skin/subcutaneous (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Tumor PD-L1 correlated with BOR if determined in LN (OR = 0.319; 95% CI = 0.138-0.762; P = 0.010), but not in skin/subcutaneous metastases (OR = 0.656; 95% CI = 0.311-1.341; P = 0.26). PD-L1 positivity determined on LN metastases was associated with favorable survival (PFS, HR = 0.490; 95% CI = 0.310-0.775; P = 0.002; OS, HR = 0.519; 95% CI = 0.307-0.880; P = 0.014). PD-L1 positivity determined in PT (PFS, HR = 0.757; 95% CI = 0.467-1.226; P = 0.27; OS; HR = 0.528; 95% CI = 0.305-0.913; P = 0.032) was correlated with survival to a lesser extent. No relevant survival differences were detected by PD-L1 determined in skin/subcutaneous metastases (PFS, HR = 0.825; 95% CI = 0.555-1.226; P = 0.35; OS, HR = 1.083; 95% CI = 0.698-1.681; P = 0.72).For PD-1-based immunotherapy in melanoma, tumor PD-L1 determined in LN metastases was stronger correlated with therapy outcome than that assessed in PT or organ metastases. PD-L1 determined in skin/subcutaneous metastases showed no outcome correlation and therefore should be used with caution for clinical decision making.Bristol-Myers Squibb (ADOREG/TRIM, NCT05750511); German Research Foundation (DFG; Clinician Scientist Program UMEA); Else Kröner-Fresenius-Stiftung (EKFS; Medical Scientist Academy UMESciA).Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.