In addition to hiding from immune cells, HPV-positive tumors actively prevent immune cells from entering the tumor microenvironment. Our foundational work has elucidated how the HPV oncoproteins dysregulate chemokines in the tumor microenvironment by epigenetically silencing CXCL14, a critical signaling molecule (chemokine) that normally recruits T cells, and boosting other proinflammatory chemokines. This chemokine dysregulation creates an immunosuppressive or "cold" tumor microenvironment and promotes metastasis. Using advanced single-cell and spatial profiling techniques, we are exploring strategies to modulate chemokine signaling, ultimately aiming to promote strong, antigen-specific antitumor responses and prevent metastasis.
