YKL-40 (also named chitinase 3 like-1 protein [CHI3L1]) is a secreted chitinase-like protein which is upregulated in cancers and suggested to have pro-tumorigenic activity. YKL-40 lacks enzymatic function, but it can bind carbohydrates such as chitin. Chitooligosaccharides (COS) derived from deacetylation and hydrolysis of chitin might be used for the blockade of YKL-40 function. Here, public single-cell RNA sequencing datasets were used to elucidate the cellular source of YKL-40 gene expression in human tumors. Fibroblasts and myeloid cells were the primary sources of YKL-40. Screening of YKL-40 gene expression in syngeneic mouse cancer models showed the highest expression in the Lewis lung carcinoma (LL2) model. LL2 was used to investigate COS monotherapy and combinations with immune checkpoint inhibitors (anti-PD-L1 and anti-CTLA-4) (ICIs) and radiotherapy (8 Gy × 3) (RT). COS tended to reduce plasma YKL-40 levels, but it did not affect tumor growth. LL2 showed minimal responses to ICIs, or to RT alone. Interestingly, ICIs combined with COS led to delayed tumor growth. RT also enhanced the efficacy of ICIs; however, the addition of COS did not further delay the tumor growth. COS may exert their anti-tumorigenic effects through the inhibition of YKL-40, but additional functions of COS should be investigated.

中文翻译：

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壳寡糖提高检查点抑制剂在肺癌小鼠模型中的功效

YKL-40（也称为几丁质酶 3 like-1 蛋白 [CHI3L1]）是一种分泌型几丁质酶样蛋白，在癌症中上调并被认为具有促肿瘤活性。YKL-40 缺乏酶促功能，但它可以结合几丁质等碳水化合物。甲壳素脱乙酰化和水解衍生的壳寡糖 (COS) 可用于阻断 YKL-40 功能。在这里，公共单细胞 RNA 测序数据集用于阐明人类肿瘤中 YKL-40 基因表达的细胞来源。成纤维细胞和骨髓细胞是 YKL-40 的主要来源。在同基因小鼠癌症模型中筛选 YKL-40 基因表达显示在 Lewis 肺癌 (LL2) 模型中表达最高。LL2 用于研究 COS 单一疗法以及与免疫检查点抑制剂（抗 PD-L1 和抗 CTLA-4）（ICIs）和放射疗法（8 Gy × 3）（RT）的组合。COS倾向于降低血浆YKL-40水平，但不影响肿瘤生长。LL2 对 ICI 或仅对 RT 的反应最小。有趣的是，ICIs 与 COS 结合会导致肿瘤生长延迟。RT 还增强了 ICI 的疗效；然而，添加 COS 并没有进一步延缓肿瘤的生长。COS 可能通过抑制 YKL-40 发挥其抗肿瘤作用，但应研究 COS 的其他功能。RT 还增强了 ICI 的疗效；然而，添加 COS 并没有进一步延缓肿瘤的生长。COS 可能通过抑制 YKL-40 发挥其抗肿瘤作用，但应研究 COS 的其他功能。RT 还增强了 ICI 的疗效；然而，添加 COS 并没有进一步延缓肿瘤的生长。COS 可能通过抑制 YKL-40 发挥其抗肿瘤作用，但应研究 COS 的其他功能。