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Review
. 2018 Nov 13;19(11):3584.
doi: 10.3390/ijms19113584.

From Friend to Enemy: Dissecting the Functional Alteration of Immunoregulatory Components during Pancreatic Tumorigenesis

Hui-Ching Wang  1   2 , Wen-Chun Hung  3 , Li-Tzong Chen  4   5 , Mei-Ren Pan  6
Affiliations
Review

From Friend to Enemy: Dissecting the Functional Alteration of Immunoregulatory Components during Pancreatic Tumorigenesis

Hui-Ching Wang et al. Int J Mol Sci. .

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a 5-year survival rate of approximately 8%. More than 80% of patients are diagnosed at an unresectable stage due to metastases or local extension. Immune system reactivation in patients by immunotherapy may eliminate tumor cells and is a new strategy for cancer treatment. The anti-CTLA-4 antibody ipilimumab and anti-PD-1 antibodies pembrolizumab and nivolumab have been approved for cancer therapy in different countries. However, the results of immunotherapy on PDAC are unsatisfactory. The low response rate may be due to poor immunogenicity with low tumor mutational burden in pancreatic cancer cells and desmoplasia that prevents the accumulation of immune cells in tumors. The immunosuppressive tumor microenvironment in PDAC is important in tumor progression and treatment resistance. Switching from an immune tolerance to immune activation status is crucial to overcome the inability of self-defense in cancer. Therefore, thoroughly elucidation of the roles of various immune-related factors, tumor microenvironment, and tumor cells in the development of PDAC may provide appropriate direction to target inflammatory pathway activation as a new therapeutic strategy for preventing and treating this cancer.

Keywords: CTLA-4; PD-1; PD-L1; immunotherapy; pancreatic cancer.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The response to immunotherapy in pancreatic ductal adenocarcinoma (PDAC) relies on destroying cancer cells as well as on breaking the stromal barrier and flaring up immune function. Immunotherapy targeting the PD-1/PD-L1 pathway and TME has disrupted the traditional method of cancer treatment and countered the immune-related adverse events in patients. In addition to direct cytotoxicity on cancer cells, it is important to dissect the immunosuppressive microenvironment with various cytokines and immune cells. Furthermore, recognition of mechanisms modulating the PD-1/PD-L1 pathway and TME will identify more potential therapeutic targets in the future.
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