Neutrophils are multifaceted innate immune cells that play a significant role in the progression of cancer by exerting both pro- and anti-tumorigenic functions. The crosstalk between cancer cells and neutrophils is complex and emerging evidence is pointing at cancer cell-intrinsic programs regulating neutrophil abundance, phenotype and function. Cancer cell-derived soluble mediators are key players in modulating the interaction with neutrophils. Here, we review how intrinsic features of cancer cells, including cancer cell genetics, epigenetics, signaling, and metabolism, manipulate neutrophil behavior and how to target these processes to impact cancer progression. A molecular understanding of cancer cell-intrinsic properties that shape the crosstalk with neutrophils will provide novel therapeutic strategies for personalized immunomodulation in cancer patients.
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