Servicio de Anatomía Patológica, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain.
Instituto Biosanitario de Salamanca (IBSAL), Salamanca, Spain.
Am J Dermatopathol. 2021 Jun 1;43(6):423-428. doi: 10.1097/DAD.0000000000001856.
The introduction of immune checkpoint inhibitors (ICI) has improved the survival outcomes of patients with advanced melanoma. To date, only a few studies have evaluated the immunohistochemical (IHC) expression of PD-1 and CTLA-4 in tumor-infiltrating lymphocytes (TILs) as predictive markers of response to ICI, most of them in the context of clinical trials. Moreover, the predictive value of PD-L1 in melanoma cells in the response to immunotherapy is unclear. The aim of our study was to assess the IHC expression of PD-L1, PD-1, and CTLA-4 in samples of patients with advanced melanoma and to establish their prognostic value as predictors of ICI response in a university hospital.
The expression of PD-L1, PD-1, and CTLA-4 was evaluated in pretreatment tumor samples in a series of 35 patients, 21 patients treated with nivolumab and 14 patients with ipilimumab in monotherapy.
In the nivolumab group, 4 tumors (19%) were positive for PD-L1 and all of them showed a partial response to the treatment. However, 4 patients whose tumors did not express PD-L1 also responded to nivolumab. PD-1 expression was not associated with better progression-free survival (PFS). In the ipilimumab group, 5 patients (35.7%) showed expression of CTLA-4. Positive cases showed a better PFS; however, one negative case responded to ipilimumab.
Nivolumab produces a better response compared with ipilimumab in patients with melanoma. The IHC expression of PD-L1 and CTLA-4 are associated with a higher response rate to nivolumab and ipilimumab, respectively, and better PFS, but the existence of responder patients with negative expression suggests that they are not adequate biomarkers to select candidate patients for ICI in the clinical practice.
免疫检查点抑制剂（ICI）的引入改善了晚期黑色素瘤患者的生存结果。迄今为止，只有少数研究评估了肿瘤浸润淋巴细胞（TIL）中 PD-1 和 CTLA-4 的免疫组化（IHC）表达作为对 ICI 反应的预测标志物，其中大多数是在临床试验的背景下进行的。此外，PD-L1 在黑色素瘤细胞中对免疫治疗反应的预测价值尚不清楚。我们的研究旨在评估晚期黑色素瘤患者样本中 PD-L1、PD-1 和 CTLA-4 的 IHC 表达，并在大学医院建立其作为 ICI 反应预测因子的预后价值。
在一系列 35 名患者的预处理肿瘤样本中评估了 PD-L1、PD-1 和 CTLA-4 的表达，其中 21 名患者接受了纳武单抗治疗，14 名患者接受了伊匹单抗单药治疗。
在纳武单抗组中，4 例肿瘤（19%）PD-L1 阳性，所有肿瘤均对治疗有部分反应。然而，4 例肿瘤不表达 PD-L1 的患者也对纳武单抗有反应。PD-1 表达与无进展生存期（PFS）无关。在伊匹单抗组中，5 例患者（35.7%）表达 CTLA-4。阳性病例显示出更好的 PFS；然而，1 例阴性病例对伊匹单抗有反应。
与伊匹单抗相比，纳武单抗在黑色素瘤患者中产生更好的反应。PD-L1 和 CTLA-4 的 IHC 表达与纳武单抗和伊匹单抗的更高反应率以及更好的 PFS 相关，但存在表达阴性的应答患者表明它们不是在临床实践中选择 ICI 候选患者的充分生物标志物。
