Nerves infiltrate the tumor microenvironment and stimulate the growth of cancer cells through the secretion of neurotransmitters. However, the contributions of nerves to the self-renewal capacity of cancer stem cells (CSCs) remain largely unknown. In this study, we found that CD133+ cancer cells were responsible for the initiation of thyroid cancer. Neurons were juxtaposed with CD133+ cells in thyroid cancer tissues. Acetylcholine, one of the most abundant neurotransmitters, promoted CD133 Y828 phosphorylation, and subsequently increased the interaction between CD133 and PI3K regulatory subunit p85, resulting in the activation of the PI3K-Akt pathway. Acetylcholine increased the self-renewal ability of CD133+ thyroid cancer cells through activation of CD133-Akt pathway. Furthermore, acetylcholine promoted the expression of the immune regulator PD-L1 through the activation of the CD133-Akt pathway, resulting in the resistance of CD133+ thyroid cancer cells to CD8+ T cells. However, acetylcholine receptor antagonist 4-DAMP blocked the positive effects of acetylcholine on the self-renewal and immune escape of CD133+ thyroid cancer cells. Taken together, these data suggest that acetylcholine increases the self-renewal and immune escape abilities of CD133+ thyroid cancer cells through the activation of the CD133-Akt pathway.

中文翻译：

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乙酰胆碱通过激活CD133-Akt途径促进CD133 +甲状腺癌细胞的自我更新和免疫逃逸。

神经通过神经递质的分泌而渗入肿瘤的微环境并刺激癌细胞的生长。然而，神经对癌症干细胞（CSCs）自我更新能力的贡献仍然未知。在这项研究中，我们发现CD133 +癌细胞与甲状腺癌的发生有关。在甲状腺癌组织中，神经元与CD133 +细胞并列。乙酰胆碱是最丰富的神经递质之一，可促进CD133 Y828磷酸化，并随后增加CD133与PI3K调节亚基p85之间的相互作用，从而激活PI3K-Akt途径。乙酰胆碱通过激活CD133-Akt途径提高了CD133 +甲状腺癌细胞的自我更新能力。此外，乙酰胆碱通过激活CD133-Akt途径来促进免疫调节剂PD-L1的表达，从而导致CD133 +甲状腺癌细胞对CD8 + T细胞产生抗性。然而，乙酰胆碱受体拮抗剂4-DAMP阻断了乙酰胆碱对CD133 +甲状腺癌细胞的自我更新和免疫逃逸的积极作用。综上所述，这些数据表明，乙酰胆碱通过激活CD133-Akt途径提高了CD133 +甲状腺癌细胞的自我更新和免疫逃逸能力。