Mirage or long-awaited oasis: reinvigorating T-cell responses in pancreatic cancer
| Autor: | Gregory B. Lesinski, Michael B. Ware, Bassel F. El-Rayes |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research T-Lymphocytes T cell medicine.medical_treatment Immunology Review Disease immunomodulation Metastasis Mice 03 medical and health sciences 0302 clinical medicine Immune system Pancreatic cancer Tumor Microenvironment medicine Animals Humans Immunology and Allergy Pharmacology Tumor microenvironment business.industry tumor escape Immunotherapy medicine.disease Survival Analysis 030104 developmental biology medicine.anatomical_structure Oncology Tumor Escape 030220 oncology & carcinogenesis Cancer research Molecular Medicine immunotherapy business Carcinoma Pancreatic Ductal |
| Zdroj: | Journal for Immunotherapy of Cancer |
| ISSN: | 2051-1426 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) is plagued by a dismal 5-year survival rate, early onset of metastasis and limited efficacy of systemic therapies. This scenario highlights the need to fervently pursue novel therapeutic strategies to treat this disease. Recent research has uncovered complicated dynamics within the tumor microenvironment (TME) of PDAC. An abundant stroma provides a framework for interactions between cancer-associated fibroblasts, suppressive myeloid cells and regulatory lymphocytes, which together create an inhospitable environment for adaptive immune responses. This accounts for the poor infiltration and exhausted phenotypes of effector T cells within pancreatic tumors. Innovative studies in genetically engineered mouse models have established that with appropriate pharmacological modulation of suppressive elements in the TME, T cells can be prompted to regress pancreatic tumors. In light of this knowledge, innovative combinatorial strategies involving immunotherapy and targeted therapies working in concert are rapidly emerging. This review will highlight recent advances in the field related to immune suppression in PDAC, emerging preclinical data and rationale for ongoing immunotherapy clinical trials. In particular, we draw attention to foundational findings involving T-cell activity in PDAC and encourage development of novel therapeutics to improve T-cell responses in this challenging disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|