Background/Objectives: Tumor cells exploit a variety of mechanisms to inhibit the immune response to lung cancer. The programmed cell death protein-1/programmed death-ligand-1 (PD-1/PD-L1) axis is frequently dysregulated in lung cancers with significant impacts on tumor growth. A sex difference has been observed in lung cancer progression and the response to PD-1/PD-L1 therapy, with the extent of benefits differing between men and women. The mechanism underlying these differences has not been fully established.Methods: In an attempt to better understand the nature of these differences, we searched the available literature for reports connecting sex specific bioactive molecules—including estrogens, progesterone, testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, leptin, and activin/inhibin—to sex differences in lung cancer and the response to PD-1/PDL-1 therapies. We then condensed this information to help generate testable hypotheses to explain the observed sex differences in lung cancer and its immunotherapies.Conclusions: From these efforts, we discovered potential roles for sex steroids, FSH, LH, prolactin, leptin, and activin/inhibin in both immune cell activity and cancer cell survival and in the response to PD-1/PD-L1 therapies.
背景/目的：肿瘤细胞利用多种机制抑制对肺癌的免疫应答。程序性细胞死亡蛋白-1/程序性死亡配体-1（PD-1/PD-L1）轴在肺癌中常发生失调，对肿瘤生长产生显著影响。肺癌进展及对PD-1/PD-L1治疗的反应存在性别差异，男性和女性的获益程度有所不同，其潜在机制尚未完全阐明。 方法：为深入理解这些差异的本质，我们检索了现有文献中关于性别特异性生物活性分子（包括雌激素、孕酮、睾酮、促卵泡激素、黄体生成素、催乳素、瘦素及激活素/抑制素）与肺癌性别差异及PD-1/PD-L1治疗反应关联性的报道。通过整合这些信息，我们构建了可验证的假说以解释观察到的肺癌及其免疫治疗中的性别差异。 结论：通过系统分析，我们发现性类固醇激素、促卵泡激素、黄体生成素、催乳素、瘦素及激活素/抑制素可能在免疫细胞活性、癌细胞存活及PD-1/PD-L1治疗反应中发挥潜在作用。
肿瘤(癌症)患者之家