CD56 阴性结外自然杀伤/T 细胞淋巴瘤：化疗联合或不联合 asparaginase 治疗 443 例患者的回顾性研究。
CD56-Negative Extranodal Natural Killer/T-Cell Lymphoma: A Retrospective Study in 443 Patients Treated by Chemotherapy With or Without Asparaginase.
机构信息
Department of Hematology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
出版信息
Front Immunol. 2022 Mar 17;13:829366. doi: 10.3389/fimmu.2022.829366. eCollection 2022.
OBJECTIVE
Extranodal natural killer/T cell lymphoma (NKTCL) is an aggressive EBV-related lymphoma, originating from NK cells or T cells. Previous study demonstrated that CD56 negative NKTCL should be recognized as a distinct subtype. In this study, the value of CD56 in NKTCL is validated in the era of asparaginase, and genomic analysis was done to dissect the differences between CD56-negative and positive NKTCL.
METHODS
443 patients with newly diagnosed NKTCL were enrolled in this retrospective study, and correlation between CD56 positivity and survival outcomes was analyzed. The gene sequencing data was downloaded (http://www.biosino.org/node/project/detail/OEP000498), and bioinformatics analysis was done to delineate the tumor microenvironment and differentially expressed genes.
RESULTS
CD56 was expressed in 337 patients (76.1%). Within a median follow-up time of 51 months, the 5-year overall survival (OS) and progression free survival (PFS) rates were 63.8% and 51.9%, respectively. For the whole cohort, patients who were CD56-positive had superior OS (5-year OS, 86.2% vs. 51.9%, p=0.019) and PFS (5-year PFS, 55.9% vs. 40.1%, p=0.016). For patients in early stage disease, CD56 positivity was associated with superior OS and PFS (p=0.008 and 0.005, respectively). In patients who received non-asparaginase-based chemotherapy, CD56-negative was associated with shorter OS and PFS (p<0.001), and in patients who received asparaginase-based chemotherapy, CD56-negative was not related to inferior OS and PFS (p=0.093 and p=0.829, respectively). The genomic analysis demonstrated that CD56 positive NKTCL probably originated from NK cells and CD56 negative NKTCL originated from T cells. CD56 positive NKTCL had significantly higher proportion of resting NK cells, activated NK cells, and activated CD8+ and CD4+ T cells in the tumor microenvironment.
CONCLUSIONS
CD56 negative NKTCL differs from CD56 positive NKTCL in both the tumor microenvironment and survival outcomes, and asparaginase-based treatment may overcome the poor prognosis brought by CD56 negativity.
目的
结外自然杀伤/T 细胞淋巴瘤（NKTCL）是一种侵袭性的 EBV 相关淋巴瘤，起源于 NK 细胞或 T 细胞。先前的研究表明，CD56 阴性 NKTCL 应被视为一种独特的亚型。在这项研究中，CD56 在 NKTCL 中的价值在 asparaginase 时代得到了验证，并进行了基因组分析，以剖析 CD56 阴性和阳性 NKTCL 之间的差异。
方法
本回顾性研究纳入了 443 例新诊断的 NKTCL 患者，分析了 CD56 阳性与生存结局的相关性。下载了基因测序数据（http://www.biosino.org/node/project/detail/OEP000498），并进行了生物信息学分析，以描绘肿瘤微环境和差异表达基因。
结果
337 例患者（76.1%）表达 CD56。中位随访时间为 51 个月，5 年总生存率（OS）和无进展生存率（PFS）分别为 63.8%和 51.9%。对于整个队列，CD56 阳性患者的 OS 更高（5 年 OS，86.2%比 51.9%，p=0.019）和 PFS（5 年 PFS，55.9%比 40.1%，p=0.016）。对于早期疾病患者，CD56 阳性与 OS 和 PFS 更高相关（p=0.008 和 0.005）。在接受非 asparaginase 为基础的化疗的患者中，CD56 阴性与较短的 OS 和 PFS 相关（p<0.001），而在接受 asparaginase 为基础的化疗的患者中，CD56 阴性与 OS 和 PFS 无明显关系（p=0.093 和 p=0.829）。基因组分析表明，CD56 阳性 NKTCL 可能起源于 NK 细胞，而 CD56 阴性 NKTCL 起源于 T 细胞。CD56 阳性 NKTCL 在肿瘤微环境中具有显著更高比例的静止 NK 细胞、激活 NK 细胞、以及激活的 CD8+和 CD4+T 细胞。
结论
CD56 阴性 NKTCL 在肿瘤微环境和生存结局方面与 CD56 阳性 NKTCL 不同，而 asparaginase 为基础的治疗可能克服 CD56 阴性带来的不良预后。
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