Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target
Pancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1287459/full |
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| author | Conner Hartupee Bolni Marius Nagalo Bolni Marius Nagalo Chiswili Y. Chabu Chiswili Y. Chabu Chiswili Y. Chabu Mulu Z. Tesfay Joycelynn Coleman-Barnett Joycelynn Coleman-Barnett John T. West Omeed Moaven Omeed Moaven Omeed Moaven |
| author_facet | Conner Hartupee Bolni Marius Nagalo Bolni Marius Nagalo Chiswili Y. Chabu Chiswili Y. Chabu Chiswili Y. Chabu Mulu Z. Tesfay Joycelynn Coleman-Barnett Joycelynn Coleman-Barnett John T. West Omeed Moaven Omeed Moaven Omeed Moaven |
| author_sort | Conner Hartupee |
| collection | DOAJ |
| description | Pancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasia is the hallmark of PDAC microenvironment that creates a physical and immunologic barrier. Stromal support cells and immunomodulatory cells face aberrant signaling by pancreatic cancer cells that shifts the complex balance of proper repair mechanisms into a state of dysregulation. The product of this dysregulation is the desmoplastic environment that encases the malignant cells leading to a dense, hypoxic environment that promotes further tumorigenesis, provides innate systemic resistance, and suppresses anti-tumor immune invasion. This desmoplastic environment combined with the immunoregulatory events that allow it to persist serve as the primary focus of this review. The physical barrier and immune counterbalance in the tumor microenvironment (TME) make PDAC an immunologically cold tumor. To convert PDAC into an immunologically hot tumor, tumor microenvironment could be considered alongside the tumor cells. We discuss the complex network of microenvironment molecular and cellular composition and explore how they can be targeted to overcome immuno-therapeutic challenges. |
| first_indexed | 2024-03-08T09:06:41Z |
| format | Article |
| id | doaj.art-b7224bf8cf1b427db5b9c4817289027f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T09:06:41Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b7224bf8cf1b427db5b9c4817289027f2024-02-01T04:37:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.12874591287459Pancreatic cancer tumor microenvironment is a major therapeutic barrier and targetConner Hartupee0Bolni Marius Nagalo1Bolni Marius Nagalo2Chiswili Y. Chabu3Chiswili Y. Chabu4Chiswili Y. Chabu5Mulu Z. Tesfay6Joycelynn Coleman-Barnett7Joycelynn Coleman-Barnett8John T. West9Omeed Moaven10Omeed Moaven11Omeed Moaven12Division of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, LA, United StatesDepartment of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United StatesThe Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United StatesDivision of Biological Sciences, University of Missouri, Columbia, MO, United StatesDepartment of Surgery, School of Medicine, University of Missouri, Columbia, MO, United StatesSiteman Cancer Center, Washington University, St. Louis, MO, United StatesDepartment of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United StatesDivision of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, LA, United StatesDepartment of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University (LSU) Health, New Orleans, LA, United StatesDepartment of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University (LSU) Health, New Orleans, LA, United StatesDivision of Surgical Oncology, Department of Surgery, Louisiana State University (LSU) Health, New Orleans, LA, United StatesDepartment of Interdisciplinary Oncology, Louisiana Cancer Research Center, Louisiana State University (LSU) Health, New Orleans, LA, United StatesLouisiana State University - Louisiana Children's Medical Center (LSU - LCMC) Cancer Center, New Orleans, LA, United StatesPancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasia is the hallmark of PDAC microenvironment that creates a physical and immunologic barrier. Stromal support cells and immunomodulatory cells face aberrant signaling by pancreatic cancer cells that shifts the complex balance of proper repair mechanisms into a state of dysregulation. The product of this dysregulation is the desmoplastic environment that encases the malignant cells leading to a dense, hypoxic environment that promotes further tumorigenesis, provides innate systemic resistance, and suppresses anti-tumor immune invasion. This desmoplastic environment combined with the immunoregulatory events that allow it to persist serve as the primary focus of this review. The physical barrier and immune counterbalance in the tumor microenvironment (TME) make PDAC an immunologically cold tumor. To convert PDAC into an immunologically hot tumor, tumor microenvironment could be considered alongside the tumor cells. We discuss the complex network of microenvironment molecular and cellular composition and explore how they can be targeted to overcome immuno-therapeutic challenges.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1287459/fullpancreatic adenocarcinomatumor microenvironmentPDAC TMEtumor immune microenvironmentimmune therapeuticscancer immunology |
| spellingShingle | Conner Hartupee Bolni Marius Nagalo Bolni Marius Nagalo Chiswili Y. Chabu Chiswili Y. Chabu Chiswili Y. Chabu Mulu Z. Tesfay Joycelynn Coleman-Barnett Joycelynn Coleman-Barnett John T. West Omeed Moaven Omeed Moaven Omeed Moaven Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target Frontiers in Immunology pancreatic adenocarcinoma tumor microenvironment PDAC TME tumor immune microenvironment immune therapeutics cancer immunology |
| title | Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target |
| title_full | Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target |
| title_fullStr | Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target |
| title_full_unstemmed | Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target |
| title_short | Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target |
| title_sort | pancreatic cancer tumor microenvironment is a major therapeutic barrier and target |
| topic | pancreatic adenocarcinoma tumor microenvironment PDAC TME tumor immune microenvironment immune therapeutics cancer immunology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1287459/full |
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