Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies
The advent of immunotherapy has transformed the treatment landscape for several human malignancies. Antibodies against immune checkpoints, such as anti-PD-1/PD-L1 and anti-CTLA-4, demonstrate durable clinical benefits in several cancer types. However, checkpoint blockade has failed to elicit effecti...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/3/440 |
| _version_ | 1797407839689375744 |
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| author | Thao N. D. Pham Mario A. Shields Christina Spaulding Daniel R. Principe Bo Li Patrick W. Underwood Jose G. Trevino David J. Bentrem Hidayatullah G. Munshi |
| author_facet | Thao N. D. Pham Mario A. Shields Christina Spaulding Daniel R. Principe Bo Li Patrick W. Underwood Jose G. Trevino David J. Bentrem Hidayatullah G. Munshi |
| author_sort | Thao N. D. Pham |
| collection | DOAJ |
| description | The advent of immunotherapy has transformed the treatment landscape for several human malignancies. Antibodies against immune checkpoints, such as anti-PD-1/PD-L1 and anti-CTLA-4, demonstrate durable clinical benefits in several cancer types. However, checkpoint blockade has failed to elicit effective anti-tumor responses in pancreatic ductal adenocarcinoma (PDAC), which remains one of the most lethal malignancies with a dismal prognosis. As a result, there are significant efforts to identify novel immune-based combination regimens for PDAC, which are typically first tested in preclinical models. Here, we discuss the utility and limitations of syngeneic and genetically-engineered mouse models that are currently available for testing immunotherapy regimens. We also discuss patient-derived xenograft mouse models, human PDAC organoids, and ex vivo slice cultures of human PDAC tumors that can complement murine models for a more comprehensive approach to predict response and resistance to immunotherapy regimens. |
| first_indexed | 2024-03-09T03:47:25Z |
| format | Article |
| id | doaj.art-7614a69db6a748988d13460e6ec3768a |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T03:47:25Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-7614a69db6a748988d13460e6ec3768a2023-12-03T14:32:22ZengMDPI AGCancers2072-66942021-01-0113344010.3390/cancers13030440Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy StudiesThao N. D. Pham0Mario A. Shields1Christina Spaulding2Daniel R. Principe3Bo Li4Patrick W. Underwood5Jose G. Trevino6David J. Bentrem7Hidayatullah G. Munshi8Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAMedical Scientist Training Program, University of Illinois, Chicago, IL 60612, USADepartment of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USADepartment of Surgery, University of Florida, Gainesville, FL 32611, USADepartment of Surgery, University of Florida, Gainesville, FL 32611, USAJesse Brown VA Medical Center, Chicago, IL 60612, USADepartment of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAThe advent of immunotherapy has transformed the treatment landscape for several human malignancies. Antibodies against immune checkpoints, such as anti-PD-1/PD-L1 and anti-CTLA-4, demonstrate durable clinical benefits in several cancer types. However, checkpoint blockade has failed to elicit effective anti-tumor responses in pancreatic ductal adenocarcinoma (PDAC), which remains one of the most lethal malignancies with a dismal prognosis. As a result, there are significant efforts to identify novel immune-based combination regimens for PDAC, which are typically first tested in preclinical models. Here, we discuss the utility and limitations of syngeneic and genetically-engineered mouse models that are currently available for testing immunotherapy regimens. We also discuss patient-derived xenograft mouse models, human PDAC organoids, and ex vivo slice cultures of human PDAC tumors that can complement murine models for a more comprehensive approach to predict response and resistance to immunotherapy regimens.https://www.mdpi.com/2072-6694/13/3/440immunotherapypancreatic cancermurine modelsgenetically-engineered mouse modelspatient-derived xenograftsorganoids |
| spellingShingle | Thao N. D. Pham Mario A. Shields Christina Spaulding Daniel R. Principe Bo Li Patrick W. Underwood Jose G. Trevino David J. Bentrem Hidayatullah G. Munshi Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies Cancers immunotherapy pancreatic cancer murine models genetically-engineered mouse models patient-derived xenografts organoids |
| title | Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies |
| title_full | Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies |
| title_fullStr | Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies |
| title_full_unstemmed | Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies |
| title_short | Preclinical Models of Pancreatic Ductal Adenocarcinoma and Their Utility in Immunotherapy Studies |
| title_sort | preclinical models of pancreatic ductal adenocarcinoma and their utility in immunotherapy studies |
| topic | immunotherapy pancreatic cancer murine models genetically-engineered mouse models patient-derived xenografts organoids |
| url | https://www.mdpi.com/2072-6694/13/3/440 |
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