%0 Journal Article
%T Targeting CDCP1 to Amplify CD8⁺ T cell Cytotoxicity via JAK/STAT Signaling in Cervical Cancer
%A Juan Carlos Ramirez
%A Diego Armando Lopez
%J Archive of International Journal of Cancer and Allied Science
%@ 3108-4834
%D 2023
%V 3
%N 2
%R 10.51847/DogwvQxwbw
%P 120-140
%X Cervical cancer continues to pose a significant global health burden. Discovering novel targets for immunotherapy could offer a valuable strategy to improve treatment outcomes. This research investigates how CUB domain-containing protein 1 (CDCP1) influences cervical cancer development and examines its promise as a target for therapy. We carried out in-depth investigations using clinical patient datasets and animal-based preclinical models to explore the link between CDCP1 levels and outcomes in cervical cancer. In parallel, we used both immunodeficient and immunocompetent mouse models to examine how CDCP1 shapes the tumor immune landscape, particularly its influence on infiltrating T lymphocytes—such as cytotoxic T cells (CTLs) and regulatory T cells (Tregs). Follow-up mechanistic experiments were conducted to uncover the signaling mechanisms behind CDCP1's role in immune regulation, highlighting its binding to the T-cell surface receptor CD6 and the resulting stimulation of the JAK-STAT pathway. Our findings indicate that elevated CDCP1 expression correlates with unfavorable prognosis and impaired T cell infiltration in cervical cancer patients. In particular, it disrupts the function of cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). At the mechanistic level, CDCP1 interacts directly with CD6 on T cells, leading to suppression of the JAK-STAT signaling pathway. Furthermore, the research shows that pharmacological inhibition of CDCP1 using 8-prenylnaringenin (8PN) significantly inhibits tumor progression in animal models while boosting antitumor immune responses. By shaping the tumor immune microenvironment, CDCP1 significantly contributes to the progression of cervical cancer. Interventions aimed at CDCP1 could represent an effective strategy to improve patient prognosis.
%U https://smerpub.com/article/targeting-cdcp1-to-amplify-cd8-t-cell-cytotoxicity-via-jakstat-signaling-in-cervical-cancer-rhncefalyvsk5yi