Combination immunotherapy for pancreatic cancer: challenges and future considerations.
| Autor: | Gössling GCL; Department of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Zhen DB; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA., Pillarisetty VG; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.; Department of Surgery, University of Washington School of Medicine, Seattle, WA, USA., Chiorean EG; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Expert review of clinical immunology [Expert Rev Clin Immunol] 2022 Nov; Vol. 18 (11), pp. 1173-1186. Date of Electronic Publication: 2022 Sep 11. |
| DOI: | 10.1080/1744666X.2022.2120471 |
| Abstrakt: | Introduction: Immune checkpoint inhibitors (ICI) have not yielded significant efficacy in pancreatic ductal adenocarcinoma (PDA), despite the role of the innate and adaptive immune systems on progression and survival. However, recently identified pathways have identified new targets and generated promising clinical investigations into promoting an effective immune-mediated antitumor response in PDA. Areas Covered: We review biological mechanisms associated with immunotherapy resistance and outline strategies for therapeutic combinations with established and novel therapies in PDA. Expert Opinion: Pancreatic cancers rarely benefit from treatment with ICI due to an immunosuppressive tumor microenvironment (TME). New understandings of factors associated with the suppressive TME include low- and poor-quality neoantigens, constrained effector T cells infiltration, and the presence of a dense, suppressive myeloid cell population. These findings have been translated into new clinical investigations evaluating novel therapies in combination with ICI and/or standard systemic chemotherapy and radiotherapy. The epithelial, immune, and stromal compartments are intricately related in PDA, and the framework for successful targeting of this disease requires a comprehensive and personalized approach. |
| Databáze: | MEDLINE |
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