Increased TIGIT expressing NK cells with dysfunctional phenotype in AML patients correlated with poor prognosis
Increased TIGIT expressing NK cells with dysfunctional phenotype in AML patients correlated with poor prognosis
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DOI：
10.1007/s00262-021-02978-5
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发表时间：
2021-06-15
影响因子：
5.8
通讯作者：
Shen, Erxia
中科院分区：
文献类型：
--
作者：
Liu, Guanfang;Zhang, Qi;Shen, Erxia
AML是成人中最常见的血液癌症，复发率高，总体生存率低。NK细胞已被证明具有根除AML原始细胞的能力，并且受损的NK细胞功能参与AML的发展和进展。免疫检查点参与各种癌症的免疫逃逸。免疫检查点阻断疗法主要针对释放CD 8（+）T细胞的功能，但NK细胞已成为新的靶点。然而，在AML患者中尚未观察到NK细胞上的免疫检查点特征。在这里，我们研究了来自AML患者的NK细胞在初始诊断时的免疫检查点表达，发现与来自健康供体的NK细胞相比，PD-1，TIGIT和TIM-3表达增加。进一步的分析显示，来自AML患者的表达TIGIT的NK细胞具有功能失调的表型，因为与TIGIT ㈠ NK细胞相比，TIGIT（+）NK细胞表现出较低的抗白血病作用、细胞因子产生和脱粒。TIGIT阻断可显著增强NK细胞的功能。此外，具有高频率TIGIT（+）NK细胞的AML患者具有较高的不良预后风险频率。进一步分析发现IL-10上调NK细胞上的TIGIT表达。因此，单独或与其他疗法组合的TIGIT阻断可能是治疗AML的潜在策略。
AML is the most common blood cancer in adults with a high relapse and an overall poor survival rate. NK cells have been demonstrated to have the capacity to eradicate AML blast, and an impaired NK cell function is involved in AML development and progression. Immune checkpoints are involved in immune escape in various cancers. Immune checkpoints blockade therapy mainly aimed to unleash CD8(+)T cells function, but NK cells have emerged as new target. However, immune checkpoints profile on NK cells has not been observed in AML patients. Here, we studied the immune checkpoints expression of NK cells from AML patients at initial diagnosis and found increased PD-1, TIGIT and TIM-3 expression compared to NK cells from healthy donors. Further analysis showed that TIGIT expressing NK cells from AML patients had a dysfunctional phenotype, as TIGIT(+)NK cells exhibit lower antileukemia effect, cytokine production and degranulation compared to TIGIT(-)NK cells. TIGIT blockade could significantly enhance the function of NK cells. Moreover, AML patients with high frequency of TIGIT(+)NK cells had higher frequency of poor prognosis risk. Further analysis found that IL-10 upregulated TIGIT expression on NK cells. Thus, TIGIT blockade alone or in combination with other therapy might be potential strategy to treat AML.