Department of Oncology, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg ~ Kimmel Institute for Cancer Immunotherapy, Baltimore, MD USA.
Melanoma and Cancer Immunology Programs, Johns Hopkins University School of Medicine, 1550 Orleans Street, Room 507, Baltimore, MD 21231 USA.
J Immunother Cancer. 2017 Mar 21;5:23. doi: 10.1186/s40425-017-0228-3. eCollection 2017.
Monoclonal antibodies that block immune regulatory proteins such as programmed death-1 (PD-1) have demonstrated remarkable efficacy in controlling the growth of multiple tumor types. Unresectable or metastatic basal cell carcinoma, however, has largely gone untested. Because PD-Ligand-1 (PD-L1) expression in other tumor types has been associated with response to anti-PD-1, we investigated the expression of PD-L1 and its association with PD-1 expression in the basal cell carcinoma tumor microenvironment. Among 40 basal cell carcinoma specimens, 9/40 (22%) demonstrated PD-L1 expression on tumor cells, and 33/40 (82%) demonstrated PD-L1 expression on tumor-infiltrating lymphocytes and associated macrophages. PD-L1 was observed in close geographic association to PD-1+ tumor infiltrating lymphocytes. Additionally, we present, here, the first report of an objective anti-tumor response to pembrolizumab (anti-PD-1) in a patient with metastatic PD-L1 (+) basal cell carcinoma, whose disease had previously progressed through hedgehog pathway-directed therapy. The patient remains in a partial response 14 months after initiation of therapy. Taken together, our findings provide a rationale for testing anti-PD-1 therapy in patients with advanced basal cell carcinoma, either as initial treatment or after acquired resistance to hedgehog pathway inhibition.
单克隆抗体阻断免疫调节蛋白，如程序性死亡受体-1（PD-1），已被证明在控制多种肿瘤类型的生长方面具有显著疗效。然而，无法切除或转移性基底细胞癌在很大程度上尚未得到验证。由于其他肿瘤类型中的 PD-Ligand-1（PD-L1）表达与抗 PD-1 反应相关，我们研究了 PD-L1 在基底细胞癌肿瘤微环境中的表达及其与 PD-1 表达的关系。在 40 例基底细胞癌标本中，有 9/40（22%）的肿瘤细胞表达 PD-L1，有 33/40（82%）的肿瘤浸润淋巴细胞和相关巨噬细胞表达 PD-L1。PD-L1 与 PD-1+肿瘤浸润淋巴细胞密切相关。此外，我们在这里首次报道了一例转移性 PD-L1（+）基底细胞癌患者对 pembrolizumab（抗 PD-1）的客观抗肿瘤反应，该患者的疾病在接受 Hedgehog 通路导向治疗后已经进展。自开始治疗以来，患者仍处于部分缓解状态 14 个月。综上所述，我们的研究结果为在晚期基底细胞癌患者中测试抗 PD-1 治疗提供了依据，无论是作为初始治疗还是在 Hedgehog 通路抑制获得性耐药后。
