Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment
Abstract Background Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in adv...
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| Format: | Article |
| Language: | English |
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BMC
2019-04-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1153-8 |
| _version_ | 1818020335309553664 |
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| author | Chin-King Looi Felicia Fei-Lei Chung Chee-Onn Leong Shew-Fung Wong Rozita Rosli Chun-Wai Mai |
| author_facet | Chin-King Looi Felicia Fei-Lei Chung Chee-Onn Leong Shew-Fung Wong Rozita Rosli Chun-Wai Mai |
| author_sort | Chin-King Looi |
| collection | DOAJ |
| description | Abstract Background Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME). Main body In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME. Conclusions It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient. |
| first_indexed | 2024-04-14T08:03:46Z |
| format | Article |
| id | doaj.art-d9cc73b40e2c4c40890540f86771ffd2 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-14T08:03:46Z |
| publishDate | 2019-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-d9cc73b40e2c4c40890540f86771ffd22022-12-22T02:04:49ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-04-0138112310.1186/s13046-019-1153-8Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironmentChin-King Looi0Felicia Fei-Lei Chung1Chee-Onn Leong2Shew-Fung Wong3Rozita Rosli4Chun-Wai Mai5School of Postgraduate Studies, International Medical UniversityMechanisms of Carcinogenesis Section (MCA), Epigenetics Group (EGE) International Agency for Research on Cancer, World Health OrganizationSchool of Pharmacy, International Medical UniversitySchool of Medicine, International Medical UniversityUPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra MalaysiaSchool of Pharmacy, International Medical UniversityAbstract Background Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no effective treatment options have demonstrated long-term benefits in advanced pancreatic cancer patients. Compared with other cancers, pancreatic cancer exhibits remarkable resistance to conventional therapy and possesses a highly immunosuppressive tumor microenvironment (TME). Main body In this review, we summarized the evidence and unique properties of TME in pancreatic cancer that may contribute to its resistance towards immunotherapies as well as strategies to overcome those barriers. We reviewed the current strategies and future perspectives of combination therapies that (1) promote T cell priming through tumor associated antigen presentation; (2) inhibit tumor immunosuppressive environment; and (3) break-down the desmoplastic barrier which improves tumor infiltrating lymphocytes entry into the TME. Conclusions It is imperative for clinicians and scientists to understand tumor immunology, identify novel biomarkers, and optimize the position of immunotherapy in therapeutic sequence, in order to improve pancreatic cancer clinical trial outcomes. Our collaborative efforts in targeting pancreatic TME will be the mainstay of achieving better clinical prognosis among pancreatic cancer patients. Ultimately, pancreatic cancer will be a treatable medical condition instead of a death sentence for a patient.http://link.springer.com/article/10.1186/s13046-019-1153-8Pancreatic cancerImmunotherapyTumor microenvironment |
| spellingShingle | Chin-King Looi Felicia Fei-Lei Chung Chee-Onn Leong Shew-Fung Wong Rozita Rosli Chun-Wai Mai Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment Journal of Experimental & Clinical Cancer Research Pancreatic cancer Immunotherapy Tumor microenvironment |
| title | Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment |
| title_full | Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment |
| title_fullStr | Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment |
| title_full_unstemmed | Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment |
| title_short | Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment |
| title_sort | therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment |
| topic | Pancreatic cancer Immunotherapy Tumor microenvironment |
| url | http://link.springer.com/article/10.1186/s13046-019-1153-8 |
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