Inflammation and pancreatic cancer: disease promoter and new therapeutic target

Abstract

Chronic inflammation has a certain impact on the carcinogenesis of the digestive organs. The characteristic tissue structure of pancreatic cancer, desmoplasia, results from inflammatory processes induced by cancer cells and stromal cells. Concerning the progression of pancreatic cancer, recent research has clarified the pivotal role of tumorstromal interaction, which promotes the development of an invasive phenotype of cancer and provides survival advantages against chemotherapeutic agents or immune surveillance. Tumor stromal cells such as pancreatic stellate cells and immune cells establish a microenvironment that protects cancer cells through complex interactions. The microenvironment of pancreatic cancer acts as a niche for pancreatic cancer stem cells from which therapy-resistance and disease recurrence develop. Inhibition of the stromal functions or restoration of the immune reaction against cancer cells has therapeutic benefits that enhance the efficacy of conventional therapies. Some of the recent advances in this field are now under evaluation in clinical settings, but many problems must be overcome to establish a radical therapy for pancreatic cancer. This review summarizes current knowledge about the tumor-promoting stromal functions, immune system modulation and therapeutic strategies targeting tumorstromal interactions in pancreatic cancer.

RNA sequencing analyses reveal novel differentially expressed genes and pathways in pancreatic cancer

“…The current study compared tumor with adjacent benign pancreatic tissues from the same PDAC patients. The upregulation of antigen presenting molecules reflect an inflammatory feature of the PDAC [35, 36]. …”

Interaction between pancreatic cancer cells and tumor‐associated macrophages promotes the invasion of pancreatic cancer cells and the differentiation and migration of macrophages

“…The desmoplastic stroma in the microenvironment of pancreatic cancer plays an important role in the progression of tumors and can recruit inflammatory cells, such as macrophages . The previous studies have shown that macrophages, particularly for M2 cells, are crucial for the pathogenesis of pancreatic cancer . In this study, we examined the potential effect of pancreatic cancer cell interaction with U937‐derived macrophages and M2 cells on the differentiation and function of macrophages and on the behaviors of PDAC in vitro .…”

Pancreatic Stellate Cells

“…As discussed earlier, human pancreatic cancer tissue exhibits significant infiltration by immune cells such as T cells, B cells, NK cells, neutrophils, and macrophages as well as myeloid-derived suppressor cells (as the name suggests, MDSCs have a largely immunosuppressive function) [128,[143][144][145]. Yet, pancreatic cancer cells appear to be able to successfully evade any attacks from these immune cells.…”

“…The desmoplastic reaction in PDAC is known to contain a prominent immune cell infiltrate [128,[143][144][145] but these cells appear to be unable to exert their immunogenic effects to destroy cancer cells. There is some evidence to suggest that PSCs may aid the process of immune evasion by cancer cells.…”