编者按：岁月不拘，时节如流。不觉间2023年已离我们远去。回首过去的一年，血液领域蓬勃发展，众多创新性研究成果登上国际舞台，给患者带来更多希望，给医生带来更大信心。
本期《肿瘤瞭望-血液时讯》特别邀请到法国巴黎大学U1163实验室 Amira Marouf教授，就有关复发或难治性结外NK/T细胞淋巴瘤（extranodal NK/T cell lymphoma，ENKTL）的相关研究进行解读分享，以期鉴往知来，更好开启2024！
《肿瘤瞭望-血液时讯》首先请您谈一下关于ENKTL的最新进展?
Amira Marouf教授：ENKTL是一种与EB病毒（Epstein-Barr virus，EBV）密切相关的独特淋巴瘤。在ENKTL瘤细胞的免疫组织化学检测（immunohistochemistry）中可以观察到EBER的阳性表达。而且，在细胞毒性检测中表现出高度染色（highly staining of cytotoxicity），也说明了其强烈的细胞毒性特征。ENKTL在欧洲较为罕见，而在亚洲和南美洲发病率较高。为了解这种地域差异，我们开展了第一项基于外显子/全基因组测序（exome/whole-genome sequencing）和靶向测序的研究。在该研究中，我们没有观察到法国人与亚洲人ENKTL患病率之间的差异。
Oncology Frontier-Hematology Frontier: could you please talk about the latest advances of extranodal NK/T cell lymphoma?
Extranodal NK/T cell lymphoma is a unique feature as a lymphoma associated constantly with EBV (Epstein-Barr virus). we can see that in immunohistochemistry by the positivity for EBER in the tumor cells. And also, it is associated with highly staining of cytotoxicity. It is a rare subset of patient in Europe, but with a high prevalence in Asia and South America. To learn about that, we performed the first study based on exome/whole-genome sequencing and then targeted sequencing. And we didn't observed differences in our cohort between French and Asian people.
《肿瘤瞭望-血液时讯》：今年您报道了一项关于抗PD1治疗复发或难治性ENKTL的大型研究，一项来自LYSA临床试验的配对队列分析（matched cohort analysis）。您能详细介绍一下该研究吗？
Amira Marouf教授：ENKTL是一种侵袭性极强的疾病，复发或难治性ENKTL患者预后极差。这也是我们正努力寻找针对这些患者新疗法的原因。近期一项研究强调了，免疫逃逸机制（尤其是PDL1的上调）在这些患者中的重要性。因此，我们评估了抗PD1（anti PD1）治疗在这些患者中的疗效。我们报道了迄今为止在法国复发或难治性ENKTL患者中，接受抗PD1治疗的最大研究队列。该研究结果显示，抗PD1单药治疗或联合化疗疗效显著，并且优于既往挽救治疗（图1）。
图1. 接受与未接受抗PD1治疗患者总生存（OS）对比
Oncology Frontier-Hematology Frontier: And our second question is about your study. This year, you have reported a study in a bigger set of antiPD1 therapy in relapse or refractory extranodal NK/T cell lymphoma, a matched cohort analysis from the LYSA. Could you talk about this study in detail?
This disease is a very aggressive disease and patient who experience relapse or refractory disease had very poor outcomes. That's why we are looking for new therapies for those patients. A recent study highlighted the importance of immune escape mechanism in this patient, especially PDL one up-regulation. That's why we assess the efficacy of anti PD one therapy in these patients.So we reported here the largest cohort of patient treated with anti PD one therapy in relapse or refractory ENKTL in France. And we showed high efficacy of anti PD one, not only as monotherapy, but rather in combination with chemotherapy, and we also showed its superiority to historical salvage therapy.
《肿瘤瞭望-血液时讯》：这项研究说明PD-1抑制剂与化疗联合使用对患者的疗效十分显著。您如何看待该研究的前景？
Amira Marouf教授：我认为未来主要有两个挑战。一个是确定可以预测对这种免疫治疗有反应或耐药性的生物标志物。另一个是免疫疗法与化疗的联合似乎比单独的免疫疗法更有效。我们有很多论据来支持这个假设，并且实验室中也有初步数据。因此我们还需要确定与这种免疫疗法相结合的最佳化疗方案，以促使其能够进入一线治疗方案。
Oncology Frontier-Hematology Frontier: This study provides important information that PD one inhibitor plus chemotherapy is highly effective for the average patient. So could you share your ideas of future research.
I think the two main challenges are to identify biomarkers, predictive of response or resistance to this type of therapy. And also, the other fact is that the combination of immunotherapy to chemotherapy seems to be more effective than immunotherapy alone. And we have many arguments to support this hypothesis and preliminary data in the lab as well. And we really need to identify what is the best chemotherapy to associate to this immunotherapy, be able to go to frontline therapy with that.
专家简介
Amira Marouf博士
法国巴黎大学（Université Paris Cité）U1163实验室