| Autor: |
Zoe C. Schmiechen, Ingunn M. Stromnes |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Immunology, Vol 11 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2020.613815 |
| Popis: |
Pancreatic ductal adenocarcinoma (PDA) is a lethal malignancy with an overall 5-year survival rate of 10%. Disease lethality is due to late diagnosis, early metastasis and resistance to therapy, including immunotherapy. PDA creates a robust fibroinflammatory tumor microenvironment that contributes to immunotherapy resistance. While previously considered an immune privileged site, evidence demonstrates that in some cases tumor antigen-specific T cells infiltrate and preferentially accumulate in PDA and are central to tumor cell clearance and long-term remission. Nonetheless, PDA can rapidly evade an adaptive immune response using a myriad of mechanisms. Mounting evidence indicates PDA interferes with T cell differentiation into potent cytolytic effector T cells via deficiencies in naive T cell priming, inducing T cell suppression or promoting T cell exhaustion. Mechanistic research indicates that immunotherapy combinations that change the suppressive tumor microenvironment while engaging antigen-specific T cells is required for treatment of advanced disease. This review focuses on recent advances in understanding mechanisms limiting T cell function and current strategies to overcome immunotherapy resistance in PDA. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
