Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer
Pancreatic ductal adenocarcinoma (PDAC) is plagued by a dismal 5-year survival rate, early onset of metastasis and limited efficacy of systemic therapies. This scenario highlights the need to fervently pursue novel therapeutic strategies to treat this disease. Recent research has uncovered complicat...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-10-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/2/e001100.full |
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| author | Gregory B Lesinski Bassel F El-Rayes Michael Brandon Ware |
| author_facet | Gregory B Lesinski Bassel F El-Rayes Michael Brandon Ware |
| author_sort | Gregory B Lesinski |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is plagued by a dismal 5-year survival rate, early onset of metastasis and limited efficacy of systemic therapies. This scenario highlights the need to fervently pursue novel therapeutic strategies to treat this disease. Recent research has uncovered complicated dynamics within the tumor microenvironment (TME) of PDAC. An abundant stroma provides a framework for interactions between cancer-associated fibroblasts, suppressive myeloid cells and regulatory lymphocytes, which together create an inhospitable environment for adaptive immune responses. This accounts for the poor infiltration and exhausted phenotypes of effector T cells within pancreatic tumors. Innovative studies in genetically engineered mouse models have established that with appropriate pharmacological modulation of suppressive elements in the TME, T cells can be prompted to regress pancreatic tumors. In light of this knowledge, innovative combinatorial strategies involving immunotherapy and targeted therapies working in concert are rapidly emerging. This review will highlight recent advances in the field related to immune suppression in PDAC, emerging preclinical data and rationale for ongoing immunotherapy clinical trials. In particular, we draw attention to foundational findings involving T-cell activity in PDAC and encourage development of novel therapeutics to improve T-cell responses in this challenging disease. |
| format | Article |
| id | doaj-art-a3e632be96e54b3ba4ebfcfc5408ed7d |
| institution | OA Journals |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-a3e632be96e54b3ba4ebfcfc5408ed7d2025-08-20T02:13:56ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-10-018210.1136/jitc-2020-001100Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancerGregory B Lesinski0Bassel F El-Rayes1Michael Brandon Ware2Hematology and Oncology, Emory University, Atlanta, Georgia, USADivision of Hematology and Oncology, Department of Medicine, O’Neal Comprehensive Cancer Center, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, USAHematology and Oncology, Emory University Winship Cancer Institute, Atlanta, Georgia, USAPancreatic ductal adenocarcinoma (PDAC) is plagued by a dismal 5-year survival rate, early onset of metastasis and limited efficacy of systemic therapies. This scenario highlights the need to fervently pursue novel therapeutic strategies to treat this disease. Recent research has uncovered complicated dynamics within the tumor microenvironment (TME) of PDAC. An abundant stroma provides a framework for interactions between cancer-associated fibroblasts, suppressive myeloid cells and regulatory lymphocytes, which together create an inhospitable environment for adaptive immune responses. This accounts for the poor infiltration and exhausted phenotypes of effector T cells within pancreatic tumors. Innovative studies in genetically engineered mouse models have established that with appropriate pharmacological modulation of suppressive elements in the TME, T cells can be prompted to regress pancreatic tumors. In light of this knowledge, innovative combinatorial strategies involving immunotherapy and targeted therapies working in concert are rapidly emerging. This review will highlight recent advances in the field related to immune suppression in PDAC, emerging preclinical data and rationale for ongoing immunotherapy clinical trials. In particular, we draw attention to foundational findings involving T-cell activity in PDAC and encourage development of novel therapeutics to improve T-cell responses in this challenging disease.https://jitc.bmj.com/content/8/2/e001100.full |
| spellingShingle | Gregory B Lesinski Bassel F El-Rayes Michael Brandon Ware Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer Journal for ImmunoTherapy of Cancer |
| title | Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer |
| title_full | Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer |
| title_fullStr | Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer |
| title_full_unstemmed | Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer |
| title_short | Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer |
| title_sort | mirage or long awaited oasis reinvigorating t cell responses in pancreatic cancer |
| url | https://jitc.bmj.com/content/8/2/e001100.full |
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