Laboratorio de Cancer Pulmonar, Departamento de Enfermedades Cronico-Degenerativas, Instituto Nacional de Enfermedades Respiratorias "Ismael Cosio Villegas", Mexico City 14080, Mexico.
Laboratorio de Quimioterapia Experimental, Departamento de Bioquimica, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico City 11340, Mexico.
Int J Mol Sci. 2024 Nov 12;25(22):12141. doi: 10.3390/ijms252212141.
CD155, also known as the poliovirus receptor (PVR), is a crucial molecule in the development and progression of cancer, as its overexpression favors immune evasion and resistance to immunotherapy. However, little is known about the mechanisms that regulate its overexpression. Proinflammatory factors produced by various cellular components of the tumor microenvironment (TME) have been associated with CD155 expression. We analyzed the effect of interleukin (IL)-6 on CD155 expression in lung adenocarcinoma. We found a positive relationship between mRNA and protein levels. This correlation was also observed in bioinformatics analysis and in biopsies and serum from patients with lung adenocarcinoma. Interestingly, lung adenocarcinoma cell lines expressing suppressor of cytokine signaling 1 (SOCS1) did not show increased CD155 levels upon IL-6 stimulation, and SOCS1 silencing reverted this effect. IL-6 and SOCS1 are critical regulators of CD155 expression in lung adenocarcinoma. Further basic and clinical studies are needed to define the role of these molecules during tumor development and to improve their clinical impact as biomarkers and targets for predicting the efficacy of immunotherapies. This study deepens the understanding of the intricate regulation of the immune checkpoints mediated by soluble factors and allows us to devise new ways to combine conventional treatments with the most innovative anticancer options.
CD155，也称为脊髓灰质炎病毒受体（PVR），是癌症发生和发展中的关键分子，因为其过表达有利于免疫逃逸和对免疫治疗的耐药性。然而，关于调节其过表达的机制知之甚少。肿瘤微环境（TME）中各种细胞成分产生的促炎因子与 CD155 的表达有关。我们分析了白细胞介素（IL）-6 对肺腺癌中 CD155 表达的影响。我们发现 mRNA 和蛋白水平之间存在正相关。这一相关性在生物信息学分析以及肺腺癌患者的活检和血清中也得到了观察。有趣的是，表达细胞因子信号转导抑制因子 1（SOCS1）的肺腺癌细胞系在 IL-6 刺激下并未显示出 CD155 水平的增加，而 SOCS1 沉默逆转了这一效应。IL-6 和 SOCS1 是肺腺癌中 CD155 表达的关键调节因子。需要进一步的基础和临床研究来确定这些分子在肿瘤发展过程中的作用，并提高它们作为生物标志物和预测免疫治疗疗效的靶点的临床应用价值。本研究加深了对可溶性因子介导的免疫检查点的复杂调控的理解，并为我们设计将传统治疗与最具创新性的抗癌选择相结合的新方法提供了依据。
