Journal
JOURNAL OF CLINICAL MEDICINE
Volume 8, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/jcm8091472
Keywords
pancreatic ductal adenocarcinoma; immune defect; immune checkpoint; myeloid cells; tumor microenvironment; stroma
Categories
Funding
- NIH [R01 CA169702, R01 CA197296]
- Viragh Foundation
- Skip Viragh Pancreatic Cancer Center at Johns Hopkins
- National Cancer Institute Specialized Programs of Research Excellence in Gastrointestinal Cancers [P50 CA062924]
- Sidney Kimmel Comprehensive Cancer Center grant [P30 CA006973]
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With the advent of cancer immunotherapies, significant advances have been made in the treatment of many tumor types including melanoma, lung cancer, squamous cell carcinoma of the head and neck, renal cell carcinoma, bladder cancer, etc. However, similar success has not been observed with the treatment of pancreatic cancer and all other immunogenic cold tumors. This prompts the need for a better understanding of the complexity of the cold tumor microenvironment (TME) of pancreatic cancer and what are truly the defects in the TME making the cancer unresponsive to immune checkpoint inhibitors. Here we discuss four major immune defects that can be recognized in pancreatic cancer, including lack of high-quality effector intratumoral T cells, heterogeneous dense stroma as a barrier to effector immune cells infiltrating into the tumor, immunosuppressive tumor microenvironment, and failure of the T cells to accomplish tumor elimination. We also discuss potential strategies for pancreatic cancer treatment that work by correcting these immune defects.
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