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.

中文翻译：

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人NKp44 +第3组先天性淋巴样细胞与大肠癌中肿瘤相关的第三级淋巴样结构相关。

先天性淋巴样细胞（ILC）负责粘膜组织稳态，并参与多种癌症的进展和抑制。然而，人们对ILC对结直肠癌的影响了解甚少。我们表征正常结肠和大肠癌组织中的人类ILC，研究其在肿瘤免疫微环境中的作用。从结肠直肠癌患者获得正常的粘膜和肿瘤组织，并通过酶消化分离细胞。NKp44 + ILC3s在正常结肠粘膜和T1 / T2肿瘤中积累了高表达与第三级淋巴样结构（TLS）形成相关的基因，包括LTA，LTB和TNF。然而，与正常结肠粘膜和T1 / T2肿瘤相比，在T3 / T4肿瘤中NKp44 + ILC3的数量显着减少。存在于T3 / T4肿瘤中的NKp44 + ILC3s减少了与TLS形成相关的基因的表达，而基质细胞减少了CXCL13，CCL19和CCL21的表达。肿瘤进展过程中NKp44 + ILC3的数量减少与肿瘤中的TLS密度相关。因此，我们的结果表明，NKp44 + ILC3s浸润了结直肠癌组织，但是T3 / T4肿瘤中的细胞数量减少，而TLS诱导的相关减少。