Tumor-associated neutrophils in pancreatic cancer progression and metastasis

Abstract

Pancreatic cancer (PC) remains a challenge to modern-day cancer therapeutics, with a dismal five-year survival rate of 12%. Due to the pancreas's location and desmoplasia surrounding it, patients receive late diagnoses and fail to respond to chemotherapy regimens. Tumor-promoting inflammation, one of the emerging hallmarks of cancer, contributes to tumor cells' survival and proliferation. This inflammation often results from infiltrating leukocytes and pro-inflammatory cytokines released into the tumor microenvironment (TME). Neutrophils, one of our body's most prominent immune cells, are essential in sustaining the inflammation observed in the TME. Recent reports demonstrate that neutrophils are complicit in cancer progression and metastasis. Additionally, abundant data suggest that tumor-associated neutrophils (TANs) could be considered as one of the emerging targets for multiple cancer types, including PC. This review will focus on the most recent updates regarding neutrophil recruitments and functions in the cancer microenvironment and the potential development of neutrophils-targeted putative therapeutic strategies in PC.

Keywords: Neutrophils; cancer progression; metastasis; neutrophil extracellular traps; neutrophil polarization.

Figure 1

Neutrophil-PDAC interaction in the microenvironment. PDAC and cancer cells interact in the tumor microenvironment (TME) in a manner that still needs to be further elucidated. PDAC cancer cells interacts with neutrophils in the TME via cytokines and growth factors to cause phenotypic change in neutrophil to become tumor associated. Neutrophils then undergo several processes - such as NETosis, Apoptosis, etc. - That causes changes in their cytokine and growth factor production. These changes in turn effect the overall progression of PDAC through various pathways that still need further exploration. Created with BioRender.com.