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Review
. 2020 Jul 1;10(7):1937-1953.
eCollection 2020.

Tumor microenvironment in chemoresistance, metastasis and immunotherapy of pancreatic cancer

Shunda Wang  1 , Yatong Li  1 , Cheng Xing  1 , Cheng Ding  1 , Hanyu Zhang  1 , Lixin Chen  1 , Lei You  1 , Menghua Dai  1 , Yupei Zhao  1
Affiliations
Review

Tumor microenvironment in chemoresistance, metastasis and immunotherapy of pancreatic cancer

Shunda Wang et al. Am J Cancer Res. .

Abstract

Pancreatic cancer (PC) is a fatal disease with high malignancy and difficult for early diagnosis. PC causes more than 400,000 patient deaths world widely and becomes the severe health problems. The tumor microenvironment (TME) is comprised of acellular stroma, pancreatic stellate cells, immune cells, and soluble factors. TME is maintained by continuous cell-matrix and cell-cell interactions. TME induced by the interaction among pancreatic cancer cells, epithelial cells and stromal cells is essential for the progression of PC and leads to resistance to chemotherapy. Components in the microenvironment can also promote the formation of connective tissue in the primary or metastatic site, or promote the metastatic ability of PC by enhancing angiogenesis, epithelial-mesenchymal transformation, and lymph angiogenesis. In addition, the TME also leaves pancreatic cancer unsusceptible to different immunotherapeutic strategies. In this review, we summarized the current knowledge about TME in PC. And the focus was placed on the role of TME in chemotherapeutic resistance and metastasis in the field of PC. And we also paid attention to the immunological therapy targeting the TME, aiming to provide the novel therapy for pancreatic cancer.

Keywords: Pancreatic cancer; chemoresistance; immunotherapy; metastasis; tumor microenvironment.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Characteristics and development of pancreatic cancer microenvironment. Pancreatic cancer microenvironment was composed by a variety of immunosuppressive cell types such as tumor-associated macrophages (TAMs), regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). Pancreatic stellate cells (PSC) and extracellular matrix (ECM) contributed to pancreatic matrix components. Cancer cells secreted cytokines and chemokines to recruit related cells for immune evasion. These different type of cells in microenvironment together with pancreatic cancer cells inhibited CD8+ T cells to escape the immune surveillance through many molecules.
Figure 2
Figure 2
The tumor microenvironment in chemoresistance and metastasis of pancreatic cancer. In pancreatic cancer, matrix forms a physical barrier for chemotherapeutic drug delivery and the hypoxic microenvironment contributes to chemoresistance. Pancreatic stellate cells and other immune cells in tumor microenvironment get together to promote chemoresistance through different cytokines and signaling pathways. Additionally, angiogenesis, EMT, lymphatic metastasis and pancreatic cancer-derived exosome in the tumor microenvironment are widely involved in pancreatic cancer metastases.
See this image and copyright information in PMC

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