Fig 5. Schema of treatment-specific histologic changes in pancreatic cancer.

Cancer tissue is composed of cancer cells and stromal fibroblasts. Chemotherapy causes damage to cancer cells, subsequently reducing the number of cancer cells and activated fibroblasts (low tumor-stroma ratio). As a result of cell death and long-lasting effects of chemotherapy, the number of activated fibroblasts decline, resulting in encapsulated mature fibrosis. When chemotherapy fails to kill cancer cells, cancer-associated fibroblasts continue to be activated, and this leads to poor prognosis. Other than fibroblasts, various cells (CD4, CD8 lymphocytes, macrophages, dendritic cells, endothelial cells, pericytes, etc.) and their crosstalk influence remnant cancer cells and sensitivity for chemotherapy.