RESUMEN
(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.
RESUMEN
The main pathogenic event caused by Schistosoma mansoni infection is characterized by a granulomatous inflammatory reaction around parasite eggs and fibrosis in the liver. We have previously shown that transplantation of bone marrow cells (BMC) promotes a reduction in liver fibrosis in chronically S. mansoni-infected mice. Here we investigated the presence and phenotype of bone marrow-derived cells in livers of S. mansoni-infected mice. During the chronic phase of infection, C57BL/6 mice had an increased number of circulating mesenchymal stem cells and endothelial progenitor cells in the peripheral blood when compared to uninfected controls. In order to investigate the fate of BMC in the liver, we generated bone marrow chimeric mice by transplanting BMC from transgenic green fluorescent protein (GFP) mice into lethally irradiated wild-type C57BL/6 mice. S. mansoni-infected chimeric mice did not demonstrate increased mortality and developed similar liver histopathological features, when compared to wild-type S. mansoni-infected mice. GFP(+) bone marrow-derived cells were found in the liver parenchyma, particularly in periportal regions. CD45(+)GFP(+) cells were found in the granulomas. Flow cytometry analysis of digested liver tissue characterized GFP(+) cells as lymphocytes, myeloid cells and stem cells. GFP(+) cells were also found in areas of collagen deposition, although rare GFP(+) cells expressed the myofibroblast cell marker α-SMA. Additionally GFP(+) endothelial cells (co-stained with von Willebrand factor) were frequently observed, while BMC-derived hepatocytes (GFP(+) albumin(+) cells) were sparsely found in the liver of chimeric mice chronically infected with S. mansoni. In conclusion, BMC are recruited to the liver during chronic experimental infection with S. mansoni and contribute to the generation of different cell types involved, not only in disease pathogenesis, but possibly in liver regeneration and repair.
