Łaniewski Paweł, Cui Haiyan, Roe Denise J, Chase Dana M, Herbst-Kralovetz Melissa M
Department of Basic Medical Sciences, College of Medicine-Phoenix, University of Arizona, Phoenix, AZ USA.
UA Cancer Center, University of Arizona, Phoenix/Tucson, AZ USA.
NPJ Precis Oncol. 2020 Aug 3;4:22. doi: 10.1038/s41698-020-0126-x. eCollection 2020.
Emerging evidence suggests that the vaginal microbiota play a role in HPV persistence and cervical neoplasia development and progression. Here we examine a broad range of immune checkpoint proteins in the cervicovaginal microenvironment across cervical carcinogenesis and explore relationships among these key immunoregulatory proteins, the microbiota composition, and genital inflammation. First, we demonstrate that immune checkpoint molecules can be measured in cervicovaginal lavages. Secondly, we identify CD40, CD27, and TIM-3 to specifically discriminate cervical cancer from other groups and CD40, CD28, and TLR2 to positively correlate to genital inflammation. Finally, PD-L1 and LAG-3 levels negatively, whereas TLR2 positively correlate to health-associated dominance. Overall, our study identifies immune checkpoint signatures associated with cervical neoplasm and illuminates the multifaceted microbiota-host immunity network in the local microenvironment. This study provides a foundation for future mechanistic studies and highlights the utility of cervicovaginal lavage profiling for predicting and monitoring response to cancer therapy.
新出现的证据表明，阴道微生物群在人乳头瘤病毒（HPV）持续感染以及宫颈癌变的发生和发展中起作用。在此，我们研究了宫颈癌发生过程中宫颈阴道微环境中广泛的免疫检查点蛋白，并探讨了这些关键免疫调节蛋白、微生物群组成和生殖器炎症之间的关系。首先，我们证明免疫检查点分子可在宫颈阴道灌洗液中检测到。其次，我们确定CD40、CD27和TIM-3可特异性区分宫颈癌与其他组，而CD40、CD28和TLR2与生殖器炎症呈正相关。最后，程序性死亡受体配体1（PD-L1）和淋巴细胞激活基因3（LAG-3）水平呈负相关，而TLR2与健康相关的优势菌群呈正相关。总体而言，我们的研究确定了与宫颈癌相关的免疫检查点特征，并阐明了局部微环境中多方面的微生物群-宿主免疫网络。本研究为未来的机制研究奠定了基础，并突出了宫颈阴道灌洗分析在预测和监测癌症治疗反应方面的效用。
