In mouse xenograft experiments with the iCCA cell line CCLP1, the simultaneous depletion of PEDF, THBS1, and THBS2 in the iCCA TME reduced tumor growth and the extent of the tumor dissemination in local lymph nodes by reducing the neo-lymphangiogenesis arising from the trans-differentiation of vascular endothelial cells towards a lymphatic phenotype. Here, THBS2 is linked to neoplasm.