Tumor-associated neutrophils crosstalk with non-cancerous components of the gastrointestinal tumor microenvironment

Gastrointestinal cancer progression is dictated by a dynamic and complex interaction between malignant cells and the non-malignant components of the tumor microenvironment. The unifying axis of this intercellular network is the functional reprogramming of stromal and immune cells. While tumor-associated neutrophils are known to play pivotal roles in gastrointestinal tissue tumorigenesis, research has rarely looked beyond their isolated functions. There is a critical gap in understanding the broader crosstalk through which neutrophils and neighboring non-malignant cells mutually alter each other's behavior to drive gastrointestinal malignancy. Here, we synthesize current knowledge regarding the interactions between neutrophils and non-malignant cellular components of the tumor microenvironment in gastrointestinal cancers, emphasizing direct cellular interactions, indirect pathways and their consequences. Ultimately, elucidating this network is critical to understanding the dynamics of gastrointestinal cancer progression, predicting treatment responses, and developing targeted and more effective therapies.