LINC00632 combines with ERα to target VISTA expression, ameliorating endometriosis progression

Endometriosis, a prevalent gynecological disease affecting women's health, involves altered immune function. This study investigates the immune checkpoint protein, V-domain immunoglobulin suppressor of T cell activation (VISTA) as a therapeutic target. In patient lesions, elevated VISTA expression correlated with reduced CD8⁺ T cell abundance. Using a 3D primary cell model, the research linked this immune suppression to a high-estrogen microenvironment and mast cell infiltration. Mechanistically, mast cell-derived LINC00632 cooperated with ERα to drive VISTA overexpression. A liposomal drug delivery system co-targeting estrogen signaling and LINC00632 successfully reduced VISTA levels, rescued CD8⁺ T cell function, and significantly inhibited lesion growth in a mouse model. This work elucidates a multicellular mechanism of immune evasion in endometriosis and demonstrates a promising combination therapeutic strategy.