Fig.7

Diagram that represents the mechanisms of lymphatic-centered immune microenvironment dynamic changes during the formation of cSCC. By adjusting YAP1/VEGFC and Piezo1, the number and function of LV were adaptable under continuous UVR. Two key periods were UVR-induced eight weeks (photoaging) and 16–18 weeks (precancerous). After 8 weeks UVR, Piezo1 expression surged. However, because to a drop in YAP1 expression, the density of LVs in UV-8w dramatically decreased. Meanwhile, the collagen arrangement loosened over time and the overall amount reduced. As a result, the lymphatic drainage function declined, which Evans Blue assay validated. Lymphatic dysfunction initiate may active CD4⁺T cells to impair lymphatic function. Additionally, UVR activated suppressive CD4⁺T cells and stopped the infiltration of antigen-specific CD8⁺T cells, ultimately suppressing cellular immunity (photoimmunosuppression). After 12 weeks of UVR, YAP1 marginally increased. YAP1 expression spiked when AK lesions occurred, increasing LV density as a result. The pace of Piezo1 reduction slowed down and began to settle into a platform. Although Piezo1 was greatly reduced in the cSCC stage, the drainage and pump functions were better than those of photoaging skin because YAP1 increased, which caused the lymphatic density to improve. In the UV-16-18w and UV-20-24w groups, the infiltration of CD8⁺T cells and CD4⁺T cells significantly increased