The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are mainly known as a combination drug to attenuate side-effects of chemotherapies. However, endogenous extra-adrenal GC have been shown to substantially regulate local immune responses within various tissues, including the lung. In this study we investigated whether primary lung tumors have maintained the capacity to synthesize GC and may thereby regulate anti-tumor immune responses. We show that several non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) cell lines express key steroidogenic enzymes and synthesize bioactive GC under steady state conditions. We also show that tumor-derived GC can inhibit splenic T cell activation, thus demonstrating their immunoregulatory potential. Moreover, steroidogenic enzymes were detected by quantitative RT-PCR and immunohistochemistry in tissue sections of different human lung tumors, further strengthening the idea that human lung carcinomas regulate their microenvironment by releasing immunoregulatory GC, which potentially contributes to immune evasion and treatment resistance.

对肺癌治疗新选择的需求不可避免地要回到基础研究。需要更好地了解肿瘤本身和肿瘤环境，尤其是与免疫系统的相互作用，以开发靶向疗法。在肺癌的背景下，糖皮质激素 (GC) 主要被称为减轻化疗副作用的联合药物。然而，内源性肾上腺外 GC 已被证明可以显着调节各种组织（包括肺）内的局部免疫反应。在这项研究中，我们调查了原发性肺肿瘤是否保持了合成 GC 的能力，并可能因此调节抗肿瘤免疫反应。我们表明，几种非小细胞肺癌 (NSCLC) 和小细胞肺癌 (SCLC) 细胞系表达关键的类固醇生成酶并在稳态条件下合成具有生物活性的 GC。我们还表明，肿瘤来源的 GC 可以抑制脾脏 T 细胞活化，从而证明它们的免疫调节潜力。此外，通过定量 RT-PCR 和免疫组织化学检测了不同人类肺部肿瘤组织切片中的类固醇生成酶，进一步强化了人类肺癌通过释放免疫调节 GC 来调节其微环境的观点，这可能有助于免疫逃避和治疗抵抗。