Amôr Nádia Ghinelli, Santos Paulo Sérgio da Silva, Campanelli Ana Paula
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.
Department of Surgery, Stomatology, Pathology, and Radiology, Bauru School of Dentistry, University of São Paulo, Bauru, Brazil.
Front Cell Dev Biol. 2021 Feb 9;9:636544. doi: 10.3389/fcell.2021.636544. eCollection 2021.
Squamous cell carcinoma (SCC) is the second most common skin cancer worldwide and, despite the relatively easy visualization of the tumor in the clinic, a sizeable number of SCC patients are diagnosed at advanced stages with local invasion and distant metastatic lesions. In the last decade, immunotherapy has emerged as the fourth pillar in cancer therapy the targeting of immune checkpoint molecules such as programmed cell-death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). FDA-approved monoclonal antibodies directed against these immune targets have provide survival benefit in a growing list of cancer types. Currently, there are two immunotherapy drugs available for cutaneous SCC: cemiplimab and pembrolizumab; both monoclonal antibodies (mAb) that block PD-1 thereby promoting T-cell activation and/or function. However, the success rate of these checkpoint inhibitors currently remains around 50%, which means that half of the patients with advanced SCC experience no benefit from this treatment. This review will highlight the mechanisms by which the immune checkpoint molecules regulate the tumor microenvironment (TME), as well as the ongoing clinical trials that are employing single or combinatory therapeutic approaches for SCC immunotherapy. We also discuss the regulation of additional pathways that might promote superior therapeutic efficacy, and consequently provide increased survival for those patients that do not benefit from the current checkpoint inhibitor therapies.
鳞状细胞癌（SCC）是全球第二常见的皮肤癌，尽管在临床上肿瘤相对易于观察，但仍有相当数量的SCC患者在晚期被诊断出有局部侵袭和远处转移病灶。在过去十年中，免疫疗法已成为癌症治疗的第四大支柱——靶向免疫检查点分子，如程序性细胞死亡蛋白1（PD-1）、程序性细胞死亡配体1（PD-L1）和细胞毒性T淋巴细胞相关蛋白4（CTLA-4）。美国食品药品监督管理局（FDA）批准的针对这些免疫靶点的单克隆抗体已在越来越多的癌症类型中提供了生存益处。目前，有两种免疫疗法药物可用于皮肤SCC：西米普利单抗和帕博利珠单抗；这两种都是阻断PD-1从而促进T细胞活化和/或功能的单克隆抗体（mAb）。然而，这些检查点抑制剂目前的成功率仍约为50%，这意味着一半的晚期SCC患者无法从这种治疗中获益。本综述将重点介绍免疫检查点分子调节肿瘤微环境（TME）的机制，以及正在进行的采用单一或联合治疗方法进行SCC免疫治疗的临床试验。我们还将讨论可能促进更高治疗效果的其他途径的调节，从而为那些无法从当前检查点抑制剂疗法中获益的患者提高生存率。
