Immune cell infiltration as an indicator of the immune microenvironment of pancreatic cancer:
This paper investigates the types of inflammatory immune cells present in the tumor bed of tissue samples from patients diagnosed with pancreatic cancer. The results of this paper show that immune cells can be used for prognostic measures (meaning they can help estimate the relative survival time of the patient). The weight that this paper carries is that it, along with other studies, are starting to show the immune response has both diagnostic and prognostic value along with targeting it for therapeutics.
This particular paper was of particular interest as it hits on how this drug can affect both angiogenesis and myeloid immune cell infiltration. The authors primarily focused on looking for decreased infiltration of macrophages and neutrophils, but there is an underlying importance here not highlighted which is the potential of this drug to inhibit infiltration of myeloid-derived suppressor cells (MDSCs). MDSCs have been shown to be potent immunoregulatory cells that highly favor tumor progression and ablating these cells could increase patient survival.
The role of neutrophils in tumorigenesis in general is a relatively new field of research as previously neutrophils were simply thought to serve as the first immune cells on the scene to recruit the “bigger guns” like macrophages and dendritic cells who in turn are responsible for the immune response generated to promote/inhibit tumorigenesis. Though we have learned a lot about the EMT process (which is necessary for metastasis), this paper shows how the neutrophils in the microenvironment induce this process.
This paper builds on the above paper in showing that the enzymes released by the neutrophils actually lead to the degradation of E-cadherin which in turn leads to the tumor cells undergoing epithelial to mesenchymal transition (EMT). Thus, this paper provides a more direct mechanism for how neutrophils effect EMT in pancreatic cancer.
This is a good comprehensive review on how the infiltrating immune cells affect tumor growth by attenuating the localized inflammatory environment surrounding the tumor to promote its growth and survival. It also highlights the complexity of the tumor microenvironment, which is something we tend to forget about.
This paper is a comprehensive analysis looking at a cohort of patient tissue samples to analyze the infiltration of neutrophils in various types of pancreatic neoplasms and shows that those tumors that have a significant number of neutrophils have a poorer prognosis than those with fewer infiltrating neutrophils.