Human papillomavirus (HPV) is the second most common infectious agent causing cancer. Persistent infection with high-risk (HR)-HPV can lead to cervical intra-epithelial neoplasia and cervical carcinomas (CC). While host immune response is necessary for viral clearance, chronic immune activation contributes to a low-grade inflammation that can ultimately lead to carcinogenesis. The micro-immunotherapy medicine (MIM) 2LPAPI®could be a valuable tool to manage the clearance of the virus and reduce the risk of developing CC. In this in vitro study, we aimed to investigate its mode of action. We showed that actives from the MIM increased the IL-6, IFN-γ, and IP-10 secretion in human peripheral blood mononuclear cells (PBMCs) exposed to peptides derived from the HPV-16 capsid (HPV16(L1)). This could reflect an increase in the immune activity toward HPV-16. At the same time, some active substances reduced the lympho-proliferation and the expression of T-cell activation markers. Finally, some of the MIM actives displayed antiproliferative effects in CC-derived HeLa cells under serum-starvation conditions. Altogether, this body of data highlighted for the first time the dual effect of MIM in the framework of HR-HPV infections as a potential (i) immune modulator of HPV16(L1)-treated PBMCs and (ii) antiproliferative agent of HPV-positive CC cells.
人乳头瘤病毒(HPV)是第二大常见致癌感染源。持续感染高危型HPV可导致宫颈上皮内瘤变及宫颈癌。虽然宿主免疫应答对病毒清除至关重要,但慢性免疫激活会引发低度炎症,最终可能导致癌变。微免疫治疗药物2LPAPI®或将成为管理病毒清除、降低宫颈癌发生风险的有效工具。本研究通过体外实验旨在探讨其作用机制。我们发现,在暴露于HPV-16衣壳衍生肽段(HPV16(L1))的人外周血单个核细胞中,该微免疫治疗药物的活性成分能提升IL-6、IFN-γ和IP-10的分泌水平,这可能反映了针对HPV-16的免疫活性增强。同时,部分活性物质能抑制淋巴细胞增殖并降低T细胞活化标志物的表达。最后,在血清饥饿条件下,某些微免疫治疗活性成分对宫颈癌来源的HeLa细胞显示出抗增殖效应。整体而言,本研究首次揭示了微免疫治疗药物在高危型HPV感染框架中的双重作用:既可作为HPV16(L1)处理的外周血单个核细胞的免疫调节剂,又能作为HPV阳性宫颈癌细胞的抗增殖剂。