(1) Background: Cervical intraepithelial neoplasia (CIN) is a precancerous condition linked to human papillomavirus (HPV) infection, often necessitating surgical interventions carrying the risk of subsequent preterm births. This study explores the potential of imiquimod (IMQ), as a non-invasive alternative treatment. The focus is on understanding IMQ impact on immune checkpoint molecules, particularly PD-1, PD-L1, and sHLA-G, which play pivotal roles in shaping immune responses and cancer progression. (2) Methods: Forty-three patients diagnosed with a high-risk squamous intraepithelial lesion (HSIL, p16-positive) self-applied 5% IMQ encapsulated in sachets containing 250 g of cream into the vaginal cavity three times a week for 16 weeks. The impact of IMQ therapy on cervical lesion regression was assessed through immunohistochemistry (IHC), examining changes in sHLA-G, PD-L1, and PD-1 levels. The antiviral activity of IMQ was evaluated through HPV-E7 immunofluorescence. Ethical considerations were adhered to, and the research methods were based on a previously approved clinical trial (clinicaltrials.gov Identifier: NCT04859361). (3) Results: IMQ treatment demonstrated efficacy, leading to lesion regression. sHLA-G levels in CIN before starting IMQ application were associated with unsuccessful treatment (p= 0.0036). IMQ did not significantly alter the expression of PD-1. We observed a decrease in PD-L1 levels in those who were successfully treated (p= 0.0509) and a reduction in HPV burden. (4) Conclusions: IMQ exhibits promise as a non-invasive treatment for CIN, emphasising its potential to modulate the immune microenvironment. Baseline sHLA-G levels emerge as potential predictors of treatment response. Understanding the nuanced dynamics of immune checkpoints sheds light on IMQ mechanism of action. Further exploration is warranted to decipher the intricate mechanisms underlying IMQ treatment in the context of cervical lesions.
（1）背景：宫颈上皮内瘤变（CIN）是一种与人乳头瘤病毒（HPV）感染相关的癌前病变，通常需要手术治疗，但手术可能导致后续早产风险。本研究探讨了咪喹莫特（IMQ）作为非侵入性替代疗法的潜力，重点关注IMQ对免疫检查点分子（尤其是PD-1、PD-L1和sHLA-G）的影响，这些分子在免疫应答和癌症进展中起关键作用。（2）方法：43例确诊为高危型鳞状上皮内病变（HSIL，p16阳性）的患者，每周三次自行将含5% IMQ的250克乳膏袋剂置入阴道腔，持续16周。通过免疫组织化学（IHC）检测sHLA-G、PD-L1和PD-1水平变化，评估IMQ治疗对宫颈病变消退的影响；通过HPV-E7免疫荧光评估IMQ的抗病毒活性。研究遵循伦理规范，方法基于先前批准的临床试验（临床试验注册号：NCT04859361）。（3）结果：IMQ治疗显示有效，可促进病变消退。治疗前CIN患者的sHLA-G水平与治疗失败相关（p=0.0036）。IMQ未显著改变PD-1表达，但在治疗成功者中观察到PD-L1水平下降（p=0.0509）及HPV负荷降低。（4）结论：IMQ作为CIN非侵入性治疗具有前景，突显其调节免疫微环境的潜力。基线sHLA-G水平可作为治疗反应的潜在预测指标。对免疫检查点动态变化的深入解析有助于阐明IMQ的作用机制，需进一步探索IMQ治疗宫颈病变的复杂机制。
肿瘤(癌症)患者之家