Gravelle Pauline, Burroni Barbara, Péricart Sarah, Rossi Cédric, Bezombes Christine, Tosolini Marie, Damotte Diane, Brousset Pierre, Fournié Jean-Jacques, Laurent Camille
Département de Pathologie, CHU Toulouse, Institut Universitaire du Cancer de Toulouse, Centre Hospitalo-Universitaire de Toulouse, Toulouse, France.
Institut Universitaire du Cancer de Toulouse, Toulouse, France.
Oncotarget. 2017 Jul 4;8(27):44960-44975. doi: 10.18632/oncotarget.16680.
Immune checkpoint blockade therapeutics, notably antibodies targeting the programmed death 1 (PD-1) receptor and its PD-L1 and PD-L2 ligands, are currently revolutionizing the treatment of cancer. For a sizeable fraction of patients with melanoma, lung, kidney and several other solid cancers, monoclonal antibodies that neutralize the interactions of the PD-1/PD-L1 complex allow the reconstitution of long-lasting antitumor immunity. In hematological malignancies this novel therapeutic strategy is far less documented, although promising clinical responses have been seen in refractory and relapsed Hodgkin lymphoma patients. This review describes our current knowledge of PD-1 and PD-L1 expression, as reported by immunohistochemical staining in both non-Hodgkin lymphoma cells and their surrounding immune cells. Here, we discuss the multiple intrinsic and extrinsic mechanisms by which both T and B cell lymphomas up-regulate the PD-1/PD-L1 axis, and review current knowledge about the prognostic significance of its immunohistochemical detection. This body of literature establishes the cell surface expression of PD-1/PD-L1 as a critical determinant for the identification of non-Hodgkin lymphoma patients eligible for immune checkpoint blockade therapies.
免疫检查点阻断疗法，尤其是靶向程序性死亡1（PD-1）受体及其PD-L1和PD-L2配体的抗体，正在彻底改变癌症的治疗方式。对于相当一部分黑色素瘤、肺癌、肾癌和其他几种实体癌患者，中和PD-1/PD-L1复合物相互作用的单克隆抗体能够重建持久的抗肿瘤免疫力。在血液系统恶性肿瘤中，这种新型治疗策略的文献报道较少，尽管在难治性和复发性霍奇金淋巴瘤患者中已观察到有前景的临床反应。本综述描述了我们目前对非霍奇金淋巴瘤细胞及其周围免疫细胞免疫组化染色所报告的PD-1和PD-L1表达的认识。在此，我们讨论T细胞和B细胞淋巴瘤上调PD-1/PD-L1轴的多种内在和外在机制，并综述目前关于其免疫组化检测预后意义的认识。这一系列文献确立了PD-1/PD-L1的细胞表面表达作为识别适合免疫检查点阻断疗法的非霍奇金淋巴瘤患者的关键决定因素。
