The RIP 1/3 promote PDAC oncogenesis and induce the immunosuppressive tumor microenvironment through both the necroptosis-induced CXCL1 and Mincle signaling; whereas, depletion of RIP 1/3, CXCL1, or Mincle protected against PDAC progression and restored anti-tumor immunity in vivo. The gene discussed is CXCL1; the disease is neoplasm.