The Trinity: Interplay among Cancer Cells, Fibroblasts, and Immune Cells in Pancreatic Cancer and Implication of CD8+ T Cell-Orientated Therapy

Abstract

The microenvironment in tumors is complicated and is constituted by different cell types and stromal proteins. Among the cell types, the abundance of cancer cells, fibroblasts, and immune cells is high and these cells work as the “Trinity” in promoting tumorigenesis. Although unidirectional or bidirectional crosstalk between two independent cell types has been well characterized, the multi-directional interplays between cancer cells, fibroblasts, and immune cells in vitro and in vivo are still unclear. We summarize recent studies in addressing the interaction of the “Trinity” members in the tumor microenvironment and propose a functional network for how these members communicate with each other. In addition, we discuss the underlying mechanisms mediating the interplay. Moreover, correlations of the alterations in the distribution and functionality of cancer cells, fibroblasts, and immune cells under different circumstances are reviewed. Finally, we point out the future application of CD8+ T cell-oriented therapy in the treatment of pancreatic cancer.

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan

“…To date, PDAC is the third leading cause of cancer mortality in the United States with a five-year survival rate of less than 12% [ 1 ]. The poor prognosis of PDAC is mainly due to delayed diagnosis, a lack of feasible detection markers, low resectability, a high recurrence rate, high resistance to chemotherapy and radiotherapy, and limited available effective therapeutic agents [ 2 ]. The mortality of major cancer types including lung cancer, breast cancer and colorectal cancer, is steadily decreasing after the introduction of novel target therapy and immunotherapy [ 3 ].…”