NKG2D-NKG2D Ligand Interaction Inhibits the Outgrowth of Naturally Arising Low-Grade B Cell Lymphoma In Vivo.
NKG2D-NKG2D Ligand Interaction Inhibits the Outgrowth of Naturally Arising Low-Grade B Cell Lymphoma In Vivo.
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DOI：
10.4049/jimmunol.1501982
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发表时间：
2016-06-01
期刊：
影响因子：
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通讯作者：
Markiewicz MA
中科院分区：
文献类型：
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作者：
Raju S;Kretzmer LZ;Koues OI;Payton JE;Oltz EM;Cashen A;Polic B;Schreiber RD;Shaw AS;Markiewicz MA
现在很清楚，免疫系统对新生肿瘤的识别对于宿主对抗癌症的生存至关重要。在癌症免疫编辑过程中，肿瘤逃避免疫识别的能力对肿瘤的发展非常重要。免疫系统通过经典抗原的存在以及保守的先天机制来识别肿瘤。其中一种机制是NKG2D受体，它识别由细胞转化诱导表达的配体。我们发现，在NKG2D受体缺乏的小鼠中，随着年龄的增长，越来越多的B细胞开始表达NKG2D配体。它们在野生型小鼠中的缺失表明这些细胞通常被表达NKG2D的细胞清除。NKG2D缺陷小鼠和组成性表达NKG2D配体的小鼠B细胞肿瘤的发生率增加，证实无法清除表达NKG2D配体的细胞在肿瘤抑制中是重要的，NKG2D配体的表达是新生肿瘤的标志。支持NKG2D配体表达在控制人类早期B细胞淋巴瘤进展中的作用，我们发现与高级别滤泡性淋巴瘤患者相比，低级别肿瘤细胞中抑制人类NKG2D配体表达的miRNA表达更高。
It is now clear that recognition of nascent tumors by the immune system is critical for survival of the host against cancer. During cancer immunoediting, the ability of the tumor to escape immune recognition is important for tumor development. The immune system recognizes tumors via the presence of classical antigens and also by conserved innate mechanisms. One of these mechanisms is the NKG2D receptor that recognizes ligands whose expression is induced by cell transformation. Here we show that in NKG2D receptor deficient mice, increasing numbers of B cells begin to express NKG2D ligands as they age. Their absence in wild-type mice suggests that these cells are normally cleared by NKG2D expressing cells. NKG2D deficient mice and mice constitutively expressing NKG2D ligands had increased incidence of B cell tumors, confirming that the inability to clear NKG2D ligand expressing cells was important in tumor suppression and that NKG2D ligand expression is a marker of nascent tumors. Supporting a role for NKG2D ligand expression in controlling the progression of early stage B cell lymphomas in humans, we found higher expression of a miRNA that inhibits human NKG2D ligand expression in tumor cells from low-grade compared with high-grade follicular lymphoma patients.