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Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review
Hong-Bo Li1, Zi-Han Yang1, Qing-Qu Guo2
1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang Province, China.
Abstract:
Pancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting. Video Abstract.
Insights
Pancreatic ductal adenocarcinoma (PDAC) is resistant to immune checkpoint inhibitors (ICIs) due to its immunosuppressive tumor microenvironment. Strategies to enhance ICI efficacy by targeting this microenvironment are under investigation.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Pancreatic ductal adenocarcinoma (PDAC) presents extremely poor prognoses, characterized by the lowest 5-year survival rates among cancers.
- Immune checkpoint inhibitors (ICIs) have shown promise in treating various solid tumors by restoring anti-tumor immune responses.
- However, PDAC exhibits limited sensitivity to ICI monotherapy, largely attributed to its immunosuppressive tumor microenvironment.
Purpose of the Study:
- To explore the intricate interactions between immune cells within the PDAC tumor microenvironment.
- To review current therapeutic strategies aimed at overcoming ICI resistance in PDAC.
- To provide insights for optimizing PDAC treatment by modulating the tumor microenvironment.
Main Methods:
- Review of existing preclinical and clinical studies on PDAC immunology.
- Analysis of the role of various immune cellular components in the PDAC microenvironment.
- Evaluation of therapeutic approaches targeting the tumor microenvironment to enhance ICI efficacy.
Main Results:
- The PDAC tumor microenvironment is characterized by complex immune cell interactions that promote immune evasion.
- Targeting specific immune suppressive elements within the microenvironment shows potential for improving ICI response.
- Combination therapies involving ICIs and microenvironment modulators are being explored.
Conclusions:
- Understanding tumor-immune cell crosstalk is crucial for developing effective PDAC therapies.
- Modulating the immunosuppressive tumor microenvironment is a promising strategy to enhance ICI efficacy in PDAC.
- Further research into combination therapies holds potential for improving patient outcomes in pancreatic cancer.
