Herein we demonstrated that NLRP4 overexpression (NLRP4-OE) served as the “key” to trigger a distinct anti-tumor ecosystem marked by the presence of TIGIT+TNFA+ NK cells and iNOS+ M1-polarised macrophages, a beneficial “lock” not reliant upon T cells (NLRP4-eco). Here, NOS2 is linked to neoplasm.