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Quantitative and Spatial Analysis of CD8+/PD-1 Tumor-Infiltrating Lymphocytes as a Predictive Biomarker for Clinical Response of Melanoma In-Transit Metastases to Topical Immunotherapy.

CD8 +/PD-1 肿瘤浸润淋巴细胞的定量和空间分析作为黑色素瘤转运中转移对局部免疫治疗临床反应的预测生物标志物。

  • 影响因子:3.60
  • DOI:10.1245/s10434-020-08713-1
  • 作者列表:"Haywood S","Garioch J","Ramaiya A","Moncrieff M
  • 发表时间:2020-06-15
Abstract

BACKGROUND:Melanoma in-transit metastases (ITMs) are a challenge to treat and associated with systemic disease and poor prognosis. Topical diphencyprone (DPCP), a potent contact sensitizer, is an established treatment for melanoma ITMs. This exploratory study investigated the utility of BRAF mutation status, CD8, PD-1, PD-L1, and TILs distribution as biomarkers for response of ITMs to topical immunotherapy (DPCP). METHODS:The ITM deposits of 40 patients treated with DPCP were subjected to biomarker analysis for BRAF status, CD8 and PD-1 expression on tumor-infiltrating lymphocytes (TILs), and tumor PD-L1 expression. Response to DPCP and overall survival (OS) were compared by biomarker status. RESULTS:After 12 weeks, 10 patients (25%) had a complete response, 12 patients (30%) had a partial response, and 18 patients (45%) had no response. No significant association was found between any individual biomarker and response to DPCP or OS. The BRAF mutation rate was 25% (10/40). All the patients with a complete response had BRAF wild-type tumor. Peritumoral CD8+ T-cells were associated with complete response (P = 0.041). Both CD8+ and PD-1 expressions were highly correlated (P < 0.0001), and the highest levels of PD-1 expression were detected at the peritumoral interface (P = 0.0004). Only two cases were PD-L1-positive, and both had a complete response to DPCP (P = 0.043). CONCLUSION:Patients who have BRAF wild-type tumor are more likely to experience a complete response to DPCP. Peritumoral TILs and PD-1 expressions may predict a better response to DPCP. Expression of PD-L1 may be associated with a complete response to DPCP. A larger prospective study is required.

摘要

背景: 黑色素瘤转运中转移 (ITMs) 是治疗的一个挑战,与全身性疾病和不良预后相关。局部易患性 (DPCP) 是一种有效的接触增敏剂,是黑色素瘤 ITMs 的既定治疗方法。本探索性研究调查了 BRAF 突变状态、 CD8 、 PD-1 、 PD-L1 和 TILs 分布作为 ITMs 对局部免疫治疗 (DPCP) 反应的生物标志物的效用。 方法: 对 40 例 DPCP 患者的 ITM 沉积物进行 BRAF 状态、肿瘤浸润淋巴细胞 (til) 上 CD8 和 PD-1 表达以及肿瘤 PD-L1 表达的生物标志物分析。通过生物标志物状态比较对 DPCP 的反应和总生存期 (OS)。 结果: 12 周后,10 例患者 (25%) 完全缓解,12 例患者 (30%) 部分缓解,18 例患者 (45%) 无反应。未发现任何个体生物标志物与对 DPCP 或 OS 的反应之间存在显著关联。BRAF 突变率为 25% (10/40)。所有完全缓解的患者均为 BRAF 野生型肿瘤。瘤周 CD8 + T 细胞与完全应答相关 (p = 0.041)。CD8 + 和 PD-1 表达高度相关 (p <0.0001),在瘤周界面检测到最高水平的 PD-1 表达 (p = 0.0004)。仅 PD-L1-positive 2 例,均对 DPCP 完全缓解 (p = 0.043)。 结论: BRAF 野生型肿瘤患者更容易对 DPCP 产生完全缓解。瘤周 TILs 和 PD-1 表达可预测 DPCP 的更好反应。PD-L1 的表达可能与 DPCP 的完全应答有关。需要更大的前瞻性研究。

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