Targeting SERPINE1, whether by inhibiting JAK2/STAT3 signaling in GC cells, blocking exosomal let-7 g-5p translocation, or disrupting STAT3 activation in macrophages, presents a novel therapeutic strategy to reprogram the immunosuppressive microenvironment, potentially transforming GC treatment through enhanced anti-tumor immunity. Here, SERPINE1 is linked to neoplasm.