Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy
Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy
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DOI：
10.1007/s00262-017-1987-x
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发表时间：
2017-07-01
影响因子：
5.8
通讯作者：
Kobayashi, Hiroya
中科院分区：
文献类型：
--
作者：
Nagato, Toshihiro;Ohkuri, Takayuki;Kobayashi, Hiroya
鼻腔自然杀伤/T细胞淋巴瘤(NNKTL)是一种治疗反应差、预后差的侵袭性肿瘤。程序性死亡-1/程序性死亡配体1(PD-1/PD-L1)通路在T细胞耗竭肿瘤细胞免疫逃避中起重要作用。本研究的目的是检测PD-L1和PD-1分子在NNKTL中的表达。我们检测了所有NNKTL患者的活检标本中PD-L1的表达。PD-L1在恶性肿瘤细胞和肿瘤浸润性巨噬细胞上均有表达，36%的患者肿瘤组织中有PD-1阳性的单个核细胞浸润。NNKTL患者血清中可溶性PD-L1(Spd-L1)水平明显高于正常人，且患者血清Spd-L1水平与肿瘤组织淋巴瘤细胞中PD-L1的表达呈正相关。此外，高Spd-L1组患者的预后明显差于低Spd-L1组。此外，我们还证实了NNKTL细胞表面和培养上清液中分别表达了膜和可溶性PD-L1。在接种NNKTL细胞系的小鼠移植瘤模型中，观察到PD-L1在肿瘤组织和血清中的表达。我们的结果表明，Spd-L1可作为NNKTL的预后预测指标，并为PD-1/PD-L1轴抑制剂免疫治疗该淋巴瘤开辟了可能性。
Nasal natural killer/T-cell lymphoma (NNKTL) is an aggressive neoplasm with poor therapeutic responses and prognosis. The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) pathway plays an important role in immune evasion of tumor cells through T-cell exhaustion. The aim of the present study was to examine the expression of PD-L1 and PD-1 molecules in NNKTL. We detected the expression of PD-L1 in biopsy samples from all of the NNKTL patients studied. PD-L1 was found on both malignant cells and tumor-infiltrating macrophages, while PD-1-positive mononuclear cells infiltrated the tumor tissues in 36% of patients. Most significantly, soluble PD-L1 (sPD-L1) was present in sera of NNKTL patients at higher levels as compared to healthy individuals and the levels of serum sPD-L1 in patients positively correlated with the expression of PD-L1 in lymphoma cells of tumor tissues. In addition, the high-sPD-L1 group of patients showed significantly worse prognosis than the low-sPD-L1 group. Furthermore, we confirmed that membrane and soluble PD-L1 was expressed on the surface and in the culture supernatant, respectively, of NNKTL cell lines. The expression of PD-L1 was observed in tumor tissues and sera from a murine xenograft model inoculated with an NNKTL cell line. Our results suggest that sPD-L1 could be a prognostic predictor for NNKTL and open up the possibility of immunotherapy of this lymphoma using PD-1/PD-L1 axis inhibitors.