Department of Clinical Medicine and Surgery, Oncology Unit, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131, Naples, Italy.
Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics, Istituto Nazionale Tumori - IRCCS - "Fondazione G. Pascale", Via Mariano Semmola, 80131, Naples, Italy.
Virchows Arch. 2019 Apr;474(4):421-432. doi: 10.1007/s00428-019-02538-4. Epub 2019 Feb 12.
Several researches have been carried over the last few decades to understand of how cancer evades the immune system and thus to identify therapies that could directly act on patient's immune system in the way of restore or induce a response to cancer. As a consequence, "cancer immunotherapy" is conquering predominantly the modern scenario of the fight against cancer. The recent clinical success of immune checkpoint inhibitors (ICIs) has created an entire new class of anti-cancer drugs and restored interest in the field of immuno-oncology, leading to regulatory approvals of several agents for the treatment of a variety of malignancies. The first to be approved in 2011 was the anti-CTLA-4 antibody ipilimumab for the treatment of unresectable or metastatic melanoma. Subsequently, the anti-PD-1s, nivolumab and pembrolizumab, received regulatory approvals for the treatment of melanoma and several other cancers. More recently, three anti-PD-L1 antibodies have received approval: atezolizumab and durvalumab for locally advanced or metastatic urothelial carcinoma and metastatic non-small cell lung cancer (NSCLC) and avelumab for the treatment of locally advanced or metastatic urothelial carcinoma and metastatic Merkel cell carcinoma. This review, starting from the results of melanoma trials, highlights in turn different ICIs and data for different indications in several malignancies are included under each drug class.
过去几十年来，已经进行了多项研究，以了解癌症如何逃避免疫系统，从而确定可以直接作用于患者免疫系统的疗法，以恢复或诱导对癌症的反应。因此，“癌症免疫疗法”正在主导着对抗癌症的现代格局。免疫检查点抑制剂（ICIs）的近期临床成功开创了一类全新的抗癌药物，并重新激发了人们对肿瘤免疫学领域的兴趣，导致批准了几种药物用于治疗多种恶性肿瘤。第一种于 2011 年获得批准的是抗 CTLA-4 抗体伊匹单抗，用于治疗不可切除或转移性黑色素瘤。随后，抗 PD-1s，nivolumab 和 pembrolizumab，获得监管批准用于治疗黑色素瘤和其他几种癌症。最近，三种抗 PD-L1 抗体已获得批准：atezolizumab 和 durvalumab 用于局部晚期或转移性尿路上皮癌和转移性非小细胞肺癌（NSCLC），avelumab 用于治疗局部晚期或转移性尿路上皮癌和转移性 Merkel 细胞癌。这篇综述从黑色素瘤试验的结果出发，依次强调了不同的 ICI，并在每种药物类别下纳入了不同适应症的不同数据。
