Barriers and opportunities in pancreatic cancer immunotherapy

Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant b...

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Bibliographic Details
Published inNPJ precision oncology Vol. 8; no. 1; pp. 199 - 18
Main Authors Ju, Yixin, Xu, Dongzhi, Liao, Miao-miao, Sun, Yutong, Bao, Wen-dai, Yao, Fan, Ma, Li
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 12.09.2024
Nature Publishing Group
Nature Portfolio
Subjects
631/67/1059/2325
692/699/67
Agriculture
Cancer Research
Cancer therapies
Chemotherapy
Dendritic cells
Gene Therapy
Granulocytes
Human Genetics
Immunotherapy
Internal Medicine
Lymphocytes
Medicine
Medicine & Public Health
Metastasis
Neutrophils
Oncology
Pancreatic cancer
Review Article
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Summary:Pancreatic ductal adenocarcinoma (PDAC) presents a fatal clinical challenge characterized by a dismal 5-year overall survival rate, primarily due to the lack of early diagnosis and limited therapeutic efficacy. Immunotherapy, a proven success in multiple cancers, has yet to demonstrate significant benefits in PDAC. Recent studies have revealed the immunosuppressive characteristics of the PDAC tumor microenvironment (TME), including immune cells with suppressive properties, desmoplastic stroma, microbiome influences, and PDAC-specific signaling pathways. In this article, we review recent advances in understanding the immunosuppressive TME of PDAC, TME differences among various mouse models of pancreatic cancer, and the mechanisms underlying resistance to immunotherapeutic interventions. Furthermore, we discuss the potential of targeting cancer cell-intrinsic pathways and TME components to sensitize PDAC to immune therapies, providing insights into strategies and future perspectives to break through the barriers in improving pancreatic cancer treatment.
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ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00681-z