Nakid-Cordero Cecilia, Baron Marine, Guihot Amélie, Vieillard Vincent
Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), INSERM U1135, CNRS ERL8285, Sorbonne Université, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
Service d'Hématologie, Groupe Hospitalier Pitié-Salpêtrière Assistance Publique-Hôpitaux de Paris (AP-HP), 75013 Paris, France.
Cancers (Basel). 2021 Apr 12;13(8):1836. doi: 10.3390/cancers13081836.
Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications arising after solid organ or hematopoietic stem cell transplantations. Although the majority of these lymphoproliferations are of B cell origin, and are frequently associated with primary Epstein-Barr virus (EBV) infection or reactivation in the post-transplant period, rare cases of T cell and natural killer (NK) cell-originated PTLDs have also been described. A general assumption is that PTLDs result from the impairment of anti-viral and anti-tumoral immunosurveillance due to the long-term use of immunosuppressants in transplant recipients. T cell impairment is known to play a critical role in the immune-pathogenesis of post-transplant EBV-linked complications, while the role of NK cells has been less investigated, and is probably different between EBV-positive and EBV-negative PTLDs. As a part of the innate immune response, NK cells are critical for protecting hosts during the early response to virus-induced tumors. The complexity of their function is modulated by a myriad of activating and inhibitory receptors expressed on cell surfaces. This review outlines our current understanding of NK cells in the pathogenesis of PTLD, and discusses their potential implications for current PTLD therapies and novel NK cell-based therapies for the containment of these disorders.
移植后淋巴细胞增生性疾病(PTLD)是实体器官或造血干细胞移植后出现的危及生命的并发症。虽然这些淋巴细胞增生大多起源于B细胞,且在移植后时期常与原发性EB病毒(EBV)感染或再激活相关,但也有罕见的T细胞和自然杀伤(NK)细胞起源的PTLD病例报道。一般认为,PTLD是由于移植受者长期使用免疫抑制剂导致抗病毒和抗肿瘤免疫监视受损所致。已知T细胞损伤在移植后EBV相关并发症的免疫发病机制中起关键作用,而NK细胞的作用研究较少,且在EBV阳性和EBV阴性PTLD中可能有所不同。作为固有免疫反应的一部分,NK细胞在对病毒诱导肿瘤的早期反应中对保护宿主至关重要。其功能的复杂性由细胞表面表达的众多激活和抑制受体调节。本综述概述了我们目前对NK细胞在PTLD发病机制中的理解,并讨论了它们对当前PTLD治疗以及基于NK细胞的新型疗法控制这些疾病的潜在意义。