CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Relationship and prognostic significance of IL-33, PD-1/PD-L1, and tertiary lymphoid structures in cervical cancer.
Relationship and prognostic significance of IL-33, PD-1/PD-L1, and tertiary lymphoid structures in cervical cancer.
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IL-33是一种上皮来源的细胞因子，在肿瘤微环境（TME）中作为免疫系统的警报素发挥作用。然而，IL-33在宫颈癌中的表达及作用仍不清楚。
本研究的目的是通过免疫组化方法，在93例宫颈癌患者标本中探讨IL-33的表达及其与临床病理特征、三级淋巴结构（TLS）以及程序性细胞死亡1（PD-1）/程序性细胞死亡1配体（PD-L1）免疫检查点的关系。与癌旁组织相比，肿瘤组织中观察到IL-33表达下调。更重要的是，IL-33在肿瘤部分的细胞质中被检测到。肿瘤细胞质中IL-33的表达与肿瘤大小和肿瘤浸润深度相关（p < 0.05）。
同时，肿瘤细胞质中IL-33的表达与肿瘤组织中CD3 + T细胞、CD8 + T细胞的浸润以及PD-L1表达呈正相关（p < 0.05）。TLS的数量与肿瘤浸润深度、术前化疗、人乳头瘤病毒感染和高水平PD-1强烈相关（p < 0.05）。
然而，IL-33与TLS之间没有显著关系。Kaplan-Meier生存曲线显示，TLS的形成与更好的预后相关（p = 0.008）。在多因素Cox回归模型中，肿瘤组织中PD-L1高表达与不良预后相关（HR = 0.128；95% CI：0.026-0.646；p = 0.013），而肿瘤组织中IL-33高表达与更好的预后相关（HR = 5.097；95% CI：1.050-24.755；p = 0.043）。这些结果表明，IL-33、TLS和PD-L1是宫颈癌潜在有价值的预后预测指标。IL-33具有与PD-L1相关抗肿瘤治疗联合应用的潜力。
IL-33, an epithelial-derived cytokine, functions as an alarmin for the immune system in the tumor microenvironment (TME).
However, the expression and role of IL-33 on cervical cancer remain unclear. The aim of this study was to investigate the expression of IL-33 and its relationship with clinicopathologic features, tertiary lymphoid structures (TLS), and programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L1) immune checkpoints by immunohistochemistry in 93 cervical cancer patient specimens. Down-regulation of IL-33 expression was observed in tumor tissues compared with adjacent tissues.
More importantly, IL-33 was detected in the cytoplasm of tumor fraction. IL-33 expression in tumor cytoplasm was associated with tumor size and the invasive depth of tumors (p < 0. 05). Meanwhile, IL-33 expression in tumor cytoplasm was positively correlated with infiltration of CD3 + T cells, CD8 + T cells, and PD-L1 expression in tumor tissues (p < 0. 05). The number of TLS strongly correlated with the depth of tumor invasion, preoperative chemotherapy, human papillomavirus infection, and high level of PD-1 (p < 0. 05).
However, there was no significant relationship between IL-33 and TLS. Kaplan-Meier survival curves showed that the formation of TLS was associated with a better prognosis (p = 0. 008). In multivariable Cox regression modeling, high expression of PD-L1 in tumor tissues was correlated with poor prognosis (HR = 0. 128; 95% CI: 0. 026-0. 646; p = 0.
013), whereas the high expression of IL-33 in tumor tissues was associated with better prognosis (HR = 5. 097; 95% CI:1. 050-24. 755; p = 0. 043). These results indicate that IL-33, TLS, and PD-L1 are potentially valuable prognostic predictor for cervical cancer. IL-33 has potential for combination with PD-L1-related antitumor therapy.
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