Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma?
The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours. Accumulating evidence relates thi...
| Main Authors: | , , , |
|---|---|
| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
Frontiers Media
2024
|
| _version_ | 1826313175508713472 |
|---|---|
| author | Smith, H Arbe-Barnes, E Shah, EA Sivakumar, S |
| author_facet | Smith, H Arbe-Barnes, E Shah, EA Sivakumar, S |
| author_sort | Smith, H |
| collection | OXFORD |
| description | The five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours. Accumulating evidence relates this resistance to its hallmark immunosuppressive milieu, which instils progressive dysfunction among tumour-infiltrating effector T cells. This milieu is established at the inception of neoplasia by immunosuppressive cellular populations, including regulatory T cells (Tregs), which accumulate in parallel with the progression to malignant PDAC. Thus, the therapeutic manipulation of Tregs has captured significant scientific and commercial attention, bolstered by the discovery that an abundance of tumour-infiltrating Tregs correlates with a poor prognosis in PDAC patients. Herein, we propose a mechanism for the resistance of PDAC to anti-PD-1 and CTLA-4 immunotherapies and re-assess the rationale for pursuing Treg-targeted therapies in light of recent studies that profiled the immune landscape of patient-derived tumour samples. We evaluate strategies that are emerging to limit Treg-mediated immunosuppression for the treatment of PDAC, and signpost early-stage trials that provide preliminary evidence of clinical activity. In this context, we find a compelling argument for investment in the ongoing development of Treg-targeted immunotherapies for PDAC. |
| first_indexed | 2024-09-25T04:09:01Z |
| format | Journal article |
| id | oxford-uuid:7c3051d4-8656-4b52-aa02-396052ecfb2d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-09-25T04:09:01Z |
| publishDate | 2024 |
| publisher | Frontiers Media |
| record_format | dspace |
| spelling | oxford-uuid:7c3051d4-8656-4b52-aa02-396052ecfb2d2024-06-13T20:05:11ZManipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7c3051d4-8656-4b52-aa02-396052ecfb2dEnglishJisc Publications RouterFrontiers Media2024Smith, HArbe-Barnes, EShah, EASivakumar, SThe five-year survival rates for pancreatic ductal adenocarcinoma (PDAC) have scarcely improved over the last half-century. It is inherently resistant to FDA-approved immunotherapies, which have transformed the outlook for patients with other advanced solid tumours. Accumulating evidence relates this resistance to its hallmark immunosuppressive milieu, which instils progressive dysfunction among tumour-infiltrating effector T cells. This milieu is established at the inception of neoplasia by immunosuppressive cellular populations, including regulatory T cells (Tregs), which accumulate in parallel with the progression to malignant PDAC. Thus, the therapeutic manipulation of Tregs has captured significant scientific and commercial attention, bolstered by the discovery that an abundance of tumour-infiltrating Tregs correlates with a poor prognosis in PDAC patients. Herein, we propose a mechanism for the resistance of PDAC to anti-PD-1 and CTLA-4 immunotherapies and re-assess the rationale for pursuing Treg-targeted therapies in light of recent studies that profiled the immune landscape of patient-derived tumour samples. We evaluate strategies that are emerging to limit Treg-mediated immunosuppression for the treatment of PDAC, and signpost early-stage trials that provide preliminary evidence of clinical activity. In this context, we find a compelling argument for investment in the ongoing development of Treg-targeted immunotherapies for PDAC. |
| spellingShingle | Smith, H Arbe-Barnes, E Shah, EA Sivakumar, S Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma? |
| title | Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma? |
| title_full | Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma? |
| title_fullStr | Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma? |
| title_full_unstemmed | Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma? |
| title_short | Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma? |
| title_sort | manipulating regulatory t cells is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma |
| work_keys_str_mv | AT smithh manipulatingregulatorytcellsisitthekeytounlockingeffectiveimmunotherapyforpancreaticductaladenocarcinoma AT arbebarnese manipulatingregulatorytcellsisitthekeytounlockingeffectiveimmunotherapyforpancreaticductaladenocarcinoma AT shahea manipulatingregulatorytcellsisitthekeytounlockingeffectiveimmunotherapyforpancreaticductaladenocarcinoma AT sivakumars manipulatingregulatorytcellsisitthekeytounlockingeffectiveimmunotherapyforpancreaticductaladenocarcinoma |