TY - JOUR
T1 - Barriers and opportunities in pancreatic cancer immunotherapy
AU - Ju, Yixin
AU - Xu, Dongzhi
AU - Liao, Miao Miao
AU - Sun, Yutong
AU - Bao, Wen Dai
AU - Yao, Fan
AU - Ma, Li
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85203834638&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85203834638&partnerID=8YFLogxK
U2 - 10.1038/s41698-024-00681-z
DO - 10.1038/s41698-024-00681-z
M3 - Review article
C2 - 39266715
AN - SCOPUS:85203834638
SN - 2397-768X
VL - 8
JO - npj Precision Oncology
JF - npj Precision Oncology
IS - 1
M1 - 199
ER -