Fig. 7

Graphical summary depicting the role of tumor-associated neutrophils in the immunosuppressive tumor microenvironment of PDAC. Neutrophils stimulated by cancer cells become the protumor phenotype through increased ER stress. Polarized tumor-associated neutrophils upregulate CCL5 secretion, which promotes cancer cell migration and invasion and enhances Treg cell infiltration in the tumor. In addition, a subpopulation of tumor-associated neutrophils upregulates Nectin2 expression, directly impeding the secretion of IFN-γ and Granzyme B by CD8⁺ T-cells through immune checkpoint signaling. Blockade of the CCL5–CCR5 axis or Nectin2 boosted CD8⁺ T-cell cytotoxicity, inhibiting tumor progression in PDAC