Human NKp44+ Group 3 Innate Lymphoid Cells Associate with Tumor-Associated Tertiary Lymphoid Structures in Colorectal Cancer
Human NKp44+ Group 3 Innate Lymphoid Cells Associate with Tumor-Associated Tertiary Lymphoid Structures in Colorectal Cancer
复制标题
人NKp44+3组先天淋巴细胞与结直肠癌肿瘤相关的三级淋巴结构
DOI：
10.1158/2326-6066.cir-19-0775
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发表时间：
2020-06-01
影响因子：
10.1
通讯作者：
Doki, Yuichiro
中科院分区：
文献类型：
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作者：
Ikeda, Atsuyo;Ogino, Takayuki;Doki, Yuichiro
先天性淋巴样细胞(ILC)负责粘膜组织的动态平衡，并参与多种类型癌症的进展和抑制。然而，ILC对结直肠癌的影响还知之甚少。我们对正常结肠和结直肠癌组织中的人类ILC进行了表征，研究了它们在肿瘤免疫微环境中的作用。取结直肠癌患者的正常粘膜和肿瘤组织，用酶消化法分离细胞。NKp44(+)ILC3高表达与三级淋巴结构(TLS)形成相关的基因，包括LTA、LTB和TNF，聚集在正常结肠粘膜和T1/T2肿瘤中。而NKp44(+)ILC3s在T3/T4肿瘤中的表达明显低于正常结肠黏膜和T1/T2肿瘤。存在于T3/T4肿瘤中的NKp44(+)ILC3降低了TLS形成相关基因的表达，而间质细胞则降低了CXCL13、CCL19和CCL21的表达。NKp44(+)ILC3在肿瘤进展过程中的减少与肿瘤中TLS的密度有关。因此，我们的结果表明，NKp44(+)ILC3在结直肠癌组织中渗透，但在T3/T4肿瘤中细胞数量减少，并伴随着TLS诱导的减少。
Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained from patients with colorectal cancer, and the cells were isolated by enzymatic digestion. NKp44(+) ILC3s with high expression of tertiary lymphoid structure (TLS) formation-related genes, including LTA, LTB, and TNF, accumulated in the normal colonic mucosa and T1/T2 tumors. However, the number of NKp44(+) ILC3s was significantly reduced in T3/T4 tumors compared with normal colonic mucosa and T1/T2 tumors. NKp44(+) ILC3s present in T3/T4 tumors had decreased expression of TLS formation-related genes, whereas stromal cells had decreased expression of CXCL13, CCL19, and CCL21. The decreasing number of NKp44(+) ILC3s during tumor progression correlated with the TLS density in tumors. Thus, our results indicate that NKp44(+) ILC3s infiltrate colorectal cancer tissue, but the number of cells decreases in T3/T4 tumors with associated decreases in TLS induction.