Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer
To date, extensive efforts to harness immunotherapeutic strategies for the treatment of pancreatic ductal adenocarcinoma (PDAC) have yielded disappointing results in clinical trials. These strategies mainly focused on cancer vaccines and immune checkpoint inhibitors alone or in combination with chem...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/16/4235 |
| _version_ | 1797524351605538816 |
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| author | Anna Maxi Wandmacher Anne Letsch Susanne Sebens |
| author_facet | Anna Maxi Wandmacher Anne Letsch Susanne Sebens |
| author_sort | Anna Maxi Wandmacher |
| collection | DOAJ |
| description | To date, extensive efforts to harness immunotherapeutic strategies for the treatment of pancreatic ductal adenocarcinoma (PDAC) have yielded disappointing results in clinical trials. These strategies mainly focused on cancer vaccines and immune checkpoint inhibitors alone or in combination with chemotherapeutic or targeted agents. However, the growing preclinical and clinical data sets from these efforts have established valuable insights into the immunological characteristics of PDAC biology. Most notable are the immunosuppressive role of the tumour microenvironment (TME) and PDAC’s characteristically poor immunogenicity resulting from tumour intrinsic features. Moreover, PDAC tumour heterogeneity has been increasingly well characterized and may additionally limit a “one-fits-all” immunotherapeutic strategy. In this review, we first outline mechanisms of immunosuppression and immune evasion in PDAC. Secondly, we summarize recently published data on preclinical and clinical efforts to establish immunotherapeutic strategies for the treatment of PDAC including diverse combinatorial treatment approaches aiming at overcoming this resistance towards immunotherapeutic strategies. Particularly, these combinatorial treatment approaches seek to concomitantly increase PDAC antigenicity, boost PDAC directed T-cell responses, and impair the immunosuppressive character of the TME in order to allow immunotherapeutic agents to unleash their full potential. Eventually, the thorough understanding of the currently available data on immunotherapeutic treatment strategies of PDAC will enable researchers and clinicians to develop improved treatment regimens and to design innovative clinical trials to overcome the pronounced immunosuppression of PDAC. |
| first_indexed | 2024-03-10T08:56:07Z |
| format | Article |
| id | doaj.art-063e09d34dca4148b7fdb218c62e4d55 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:56:07Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-063e09d34dca4148b7fdb218c62e4d552023-11-22T07:05:49ZengMDPI AGCancers2072-66942021-08-011316423510.3390/cancers13164235Challenges and Future Perspectives of Immunotherapy in Pancreatic CancerAnna Maxi Wandmacher0Anne Letsch1Susanne Sebens2Department of Internal Medicine II, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyDepartment of Internal Medicine II, University Medical Center Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyInstitute for Experimental Cancer Research, Kiel University and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyTo date, extensive efforts to harness immunotherapeutic strategies for the treatment of pancreatic ductal adenocarcinoma (PDAC) have yielded disappointing results in clinical trials. These strategies mainly focused on cancer vaccines and immune checkpoint inhibitors alone or in combination with chemotherapeutic or targeted agents. However, the growing preclinical and clinical data sets from these efforts have established valuable insights into the immunological characteristics of PDAC biology. Most notable are the immunosuppressive role of the tumour microenvironment (TME) and PDAC’s characteristically poor immunogenicity resulting from tumour intrinsic features. Moreover, PDAC tumour heterogeneity has been increasingly well characterized and may additionally limit a “one-fits-all” immunotherapeutic strategy. In this review, we first outline mechanisms of immunosuppression and immune evasion in PDAC. Secondly, we summarize recently published data on preclinical and clinical efforts to establish immunotherapeutic strategies for the treatment of PDAC including diverse combinatorial treatment approaches aiming at overcoming this resistance towards immunotherapeutic strategies. Particularly, these combinatorial treatment approaches seek to concomitantly increase PDAC antigenicity, boost PDAC directed T-cell responses, and impair the immunosuppressive character of the TME in order to allow immunotherapeutic agents to unleash their full potential. Eventually, the thorough understanding of the currently available data on immunotherapeutic treatment strategies of PDAC will enable researchers and clinicians to develop improved treatment regimens and to design innovative clinical trials to overcome the pronounced immunosuppression of PDAC.https://www.mdpi.com/2072-6694/13/16/4235PDACimmunosuppressiontumour microenvironmentcancer vaccinecheckpoint inhibitiontranslational research |
| spellingShingle | Anna Maxi Wandmacher Anne Letsch Susanne Sebens Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer Cancers PDAC immunosuppression tumour microenvironment cancer vaccine checkpoint inhibition translational research |
| title | Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer |
| title_full | Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer |
| title_fullStr | Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer |
| title_full_unstemmed | Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer |
| title_short | Challenges and Future Perspectives of Immunotherapy in Pancreatic Cancer |
| title_sort | challenges and future perspectives of immunotherapy in pancreatic cancer |
| topic | PDAC immunosuppression tumour microenvironment cancer vaccine checkpoint inhibition translational research |
| url | https://www.mdpi.com/2072-6694/13/16/4235 |
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