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Human NKp44+ group 3 innate lymphoid cells associate with tumor-associated tertiary lymphoid structures in colorectal cancer.

人 NKp44 + 第 3 组固有淋巴细胞与结直肠癌中肿瘤相关三级淋巴结构相关。

  • 影响因子:8.58
  • DOI:10.1158/2326-6066.CIR-19-0775
  • 作者列表:"Ikeda A","Ogino T","Kayama H","Okuzaki D","Nishimura J","Fujino S","Miyoshi N","Takahashi H","Uemura M","Matsuda C","Yamamoto H","Takeda K","Mizushima T","Mori M","Doki Y
  • 发表时间:2020-03-30
Abstract

:Innate lymphoid cells (ILCs) 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 (CRC) are poorly understood. We characterized human ILCs in normal colon and CRC tissue, investigating their role in the tumor immune microenvironment. Normal mucosa and tumor tissues were obtained from CRC patients 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 to 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 CRC tissue but the number of cells decreases in T3/T4 tumors, with associated decreases in TLS induction.

摘要

: 固有淋巴细胞 (ILCs) 负责粘膜组织稳态,参与几种类型癌症的进展和抑制。然而,ILCs 对结直肠癌 (CRC) 的影响知之甚少。我们对正常结肠和 CRC 组织中的人 ILCs 进行了表征,研究了它们在肿瘤免疫微环境中的作用。取 CRC 患者正常黏膜和肿瘤组织,酶消化法分离细胞。NKp44 + ILC3s 高表达三级淋巴结构 (TLS) 形成相关基因,包括 LTA 、 LTB 和 TNF,积累在正常结肠黏膜和 T1/T2 肿瘤中。然而,与正常结肠黏膜和 T1/T2 肿瘤相比,T3/T4 肿瘤中 NKp44 + ILC3s 的数量显著减少。存在于 T3/T4 肿瘤中的 NKp44 + ILC3s 具有 TLS 形成相关基因的表达降低,而基质细胞具有 CXCL13 、 CCL19 和 ccl21 的表达降低。肿瘤进展过程中 NKp44 + ILC3s 数量的减少与肿瘤中的 TLS 密度相关。因此,我们的结果表明 NKp44 + ILC3s 浸润 CRC 组织,但 T3/T4 肿瘤中细胞数量减少,TLS 诱导相关减少。

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