Cytokine modulation of PMN intratumoral recruitment and functions.

Cytokine modulation of PMN intratumoral recruitment and functions results in tumor destruction and an antitumor immune memory. Tumor-associated macrophages are the first reactive cells ready to respond to the secondary mediators (IL-1β, TNF-α, IFN-γ, etc) induced by the cytokine systemically administered or locally released by engineered tumor cells. Depending on the cytokines present in the microenvironment, activated macrophages release ELR (glutamic acid–leucine–arginine)⁺ CXC chemokines, which recruit neutrophils, and/or ELR⁻ CXC chemokines, which recruit T lymphocytes. If IL-1β and TNF-α prevail, macrophages and PMNs are induced to produce ELR⁺ chemokines (MIP-2/GRO/KC), which amplify accumulation of PMNs and favor their destructive functions. If IFN-γ prevails, they are induced to produce angiostatic ELR⁻ chemokines (interferon inducible protein-10 [IP-10], monokine induced by gamma interferon [MIG]) that recruit T lymphocytes and promote the establishment of an antitumor immune memory.