Schadendorf Dirk, Nghiem Paul, Bhatia Shailender, Hauschild Axel, Saiag Philippe, Mahnke Lisa, Hariharan Subramanian, Kaufman Howard L
Department of Dermatology, Essen University Hospital, Germany and German Cancer Consortium Partner Site Essen/Düsseldorf, Essen, Germany.
Department of Medicine, University of Washington Medical Center, Seattle, WA, USA.
Oncoimmunology. 2017 Aug 31;6(10):e1338237. doi: 10.1080/2162402X.2017.1338237. eCollection 2017.
Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance. Unlike chemotherapy, treatment with anti-PD-L1 (avelumab) or anti-PD-1 (pembrolizumab) antibodies leads to durable responses in MCC, in both virus-positive and virus-negative tumors. As many tumors are established through the evasion of infiltrating immune-cell clearance, the lessons learned in MCC may be broadly relevant to many cancers.
默克尔细胞癌(MCC)是一种由默克尔细胞多瘤病毒(MCPyV)感染和/或紫外线辐射诱导的体细胞突变引起的罕见皮肤癌。肿瘤浸润淋巴细胞的存在表明,一些患者对MCPyV和肿瘤相关新抗原发生了活跃的免疫反应。然而,MCC肿瘤微环境中的抑制性免疫分子,包括程序性死亡蛋白1(PD-1)和程序性死亡配体1(PD-L1),有助于肿瘤逃避T细胞介导的清除。与化疗不同,抗PD-L1(阿维鲁单抗)或抗PD-1(帕博利珠单抗)抗体治疗在病毒阳性和病毒阴性肿瘤的MCC中均能产生持久反应。由于许多肿瘤是通过逃避浸润免疫细胞的清除而形成的,因此在MCC中获得的经验教训可能与许多癌症广泛相关。