Tsirigotis Panagiotis, Savani Bipin N, Nagler Arnon
a Second Department of Internal Medicine , National and Kapodistrian University of Athens , Athens , Greece.
b Department of Hematology, Vanderbilt University Medical Center , Nashville , TN , USA.
Ann Med. 2016 Sep;48(6):428-439. doi: 10.1080/07853890.2016.1186827. Epub 2016 May 25.
The use of tumor-specific monoclonal antibodies (MAbs) has revolutionize the field of cancer immunotherapy. Although treatment of malignant diseases with MAbs is promising, many patients fail to respond or relapse after an initial response. Both solid tumors and hematological malignancies develop mechanisms that enable them to evade the host immune system by usurping immune checkpoint pathways such as PD-1, PD-2, PDL-1, or PDL-2 (programmed cell death protein-1 or 2 and PD-Ligand 1 or 2), which are expressed on activated T cells and on T-regulatory, B cells, natural killers, monocytes, and dendritic cells. One of the most exciting anticancer development in recent years has been the immune checkpoint blockade therapy by using MAbs against immune checkpoint receptor and/or ligands. Anti-PD1 antibodies have been tested in clinical studies that included patients with hematological malignancies and showed remarkable efficacy in Hodgkin lymphoma (HL). In our review, we will focus on the effect of PD-1 activation on hematological malignancies and its role as a therapeutic target. Key messages The programmed death 1 (PD1) immune checkpoint is an important homeostatic mechanism of the immune system that helps in preventing autoimmunity and uncontrolled inflammation in cases of chronic infections. However, PD1 pathway is also operated by a wide variety of malignancies and represents one of the most important mechanisms by which tumor cells escape from the surveillance of the immune system. Blocking of immune checkpoints by the use of monoclonal antibodies opened a new era in the field of cancer immunotherapy. Results from clinical trials are promising, and currently, this approach has been proven effective and safe in patients with solid tumors and hematological malignancies.
肿瘤特异性单克隆抗体(MAbs)的应用彻底改变了癌症免疫治疗领域。尽管用单克隆抗体治疗恶性疾病前景广阔,但许多患者在初始反应后无反应或复发。实体瘤和血液系统恶性肿瘤都发展出了一些机制,使它们能够通过篡夺免疫检查点通路(如程序性死亡蛋白1或2、程序性死亡配体1或2,即PD-1、PD-2、PDL-1或PDL-2)来逃避宿主免疫系统,这些通路在活化的T细胞以及T调节细胞、B细胞、自然杀伤细胞、单核细胞和树突状细胞上表达。近年来最令人兴奋的抗癌进展之一是通过使用针对免疫检查点受体和/或配体的单克隆抗体进行免疫检查点阻断治疗。抗PD1抗体已在包括血液系统恶性肿瘤患者的临床研究中进行了测试,并在霍奇金淋巴瘤(HL)中显示出显著疗效。在我们的综述中,我们将重点关注PD-1激活对血液系统恶性肿瘤的影响及其作为治疗靶点的作用。关键信息 程序性死亡1(PD1)免疫检查点是免疫系统的一种重要稳态机制,有助于预防自身免疫和慢性感染情况下的不受控制的炎症。然而,PD1通路也被多种恶性肿瘤利用,是肿瘤细胞逃避免疫系统监视的最重要机制之一。使用单克隆抗体阻断免疫检查点开启了癌症免疫治疗领域的新时代。临床试验结果很有前景,目前,这种方法已被证明对实体瘤和血液系统恶性肿瘤患者有效且安全。