PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma
PD-L1/L2 protein levels rapidly increase on monocytes via trogocytosis from tumor cells in classical Hodgkin lymphoma
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DOI：
10.1038/s41375-020-0737-9
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发表时间：
2020-02-24
期刊：
影响因子：
11.4
通讯作者：
Kotani, Ai
中科院分区：
文献类型：
--
作者：
Kawashima, Masaharu;Carreras, Joaquim;Kotani, Ai
在典型的霍奇金淋巴瘤（cHL）中，肿瘤相关巨噬细胞（TAM）在肿瘤形成中起着关键作用，其特征在于存在霍奇金和里德-斯滕伯格（HRS）细胞。然而，HRS细胞和TAM之间直接接触的意义尚未阐明。已知HRS细胞和TAM表达PD-L1，导致cHL中PD-1（+）CD 4（+）T细胞耗尽。在这里，我们发现PD-L1/L2表达在与HRS细胞共培养的单核细胞中在1小时内升高，但在与HRS细胞上清液培养的单核细胞中没有升高。PD-L1/L2的免疫荧光分析显示，它们的上调导致从HRS细胞到单核细胞的称为“胞刺”的膜转移。在与PD-L1/L2缺陷型HRS细胞共培养的单核细胞中未观察到PD-L1/L2上调，验证了PD-L1/L2从HRS细胞直接转移至单核细胞的假设。在患者中，两种配体（PD-L1/L2）在与HRS细胞接触的TAM中上调，但在远离HRS细胞的TAM中未上调，这表明cHL患者中发生胞啃。总之，胞啃作用可能是诱导单核细胞中PD-L1/L2快速上调以通过MHC抗原呈递介导的T细胞抑制来逃避抗肿瘤免疫的机制之一。
In classical Hodgkin lymphoma (cHL)-characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells-tumor-associated macrophages (TAMs) play a pivotal role in tumor formation. However, the significance of direct contact between HRS cells and TAMs has not been elucidated. HRS cells and TAMs are known to express PD-L1, which leads to PD-1(+) CD4(+) T cell exhaustion in cHL. Here, we found that PD-L1/L2 expression was elevated in monocytes co-cultured with HRS cells within 1 h, but not in monocytes cultured with supernatants of HRS cells. Immunofluorescence analysis of PD-L1/L2 revealed that their upregulation resulted in membrane transfer called "trogocytosis" from HRS cells to monocytes. PD-L1/L2 upregulation was not observed in monocytes co-cultured with PD-L1/L2-deficient HRS cells, validating the hypothesis that there is a direct transfer of PD-L1/L2 from HRS cells to monocytes. In the patients, both ligands (PD-L1/L2) were upregulated in TAMs in contact with HRS cells, but not in TAMs distant from HRS cells, suggesting that trogocytosis occurs in cHL patients. Taken together, trogocytosis may be one of the mechanisms that induces rapid upregulation of PD-L1/L2 in monocytes to evade antitumor immunity through the suppression of T cells as mediated by MHC antigen presentation.