Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused CD47-SIRPα Expression
| Autor: | Ioannis S. Pateras, Ioannis I Moustakas, Timokratis Karamitros, Teresa Frisan, Sophia Havaki, Sofia D.P. Theodorou, Maria Lopez Chiloeches, Michail Vailas, Evangelos Felekouras, Eleni Patsea, Konstantinos Ntostoglou, Natasha Hasemaki, Anna Bergonzini, Niki V. Chouliari, Stratigoula Sakellariou, Antonios Chatzigeorgiou, Alexandros Papalampros, Christos Kittas, Lysandros Karydakis, Vassilis G. Gorgoulis, Paraskevi D Veltsista, Menelaos G Samaras, Andreas C. Lazaris, Aggelos Margetis |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research endocrine system diseases signal regulatory protein alpha (SIRPα) T cell Cell- och molekylärbiologi Cell pancreatic ductal adenocarcinoma Biology lcsh:RC254-282 Article Type 2 immune response 03 medical and health sciences 0302 clinical medicine Immune system draining lymph nodes Parenchyma medicine tumor microenvironment CD47 T cell exhaustion macrophage checkpoint Tumor microenvironment spatial heterogeneity T cell senescence lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Phenotype digestive system diseases 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Cancer research Cell and Molecular Biology neoadjuvant chemotherapy |
| Zdroj: | Cancers Volume 12 Issue 7 Cancers, Vol 12, Iss 1825, p 1825 (2020) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers12071825 |
| Popis: | Background: Pancreatic ductal adenocarcinoma (PDAC) is resistant to single-agent immunotherapies. To understand the mechanisms leading to the poor response to this treatment, a better understanding of the PDAC immune landscape is required. The present work aims to study the immune profile in PDAC in relationship to spatial heterogeneity of the tissue microenvironment (TME) in intact tissues. Methods: Serial section and multiplex in situ analysis were performed in 42 PDAC samples to assess gene and protein expression at single-cell resolution in the: a) tumor center (TC), b) invasive front (IF), c) normal parenchyma adjacent to the tumor, and d) tumor positive and negative draining lymph nodes (LNs). Results: We observed: a) enrichment of T cell subpopulations with exhausted and senescent phenotype in the TC, IF and tumor positive LNs b) a dominant type 2 immune response in the TME, which is more pronounced in the TC c) an emerging role of CD47-SIRP&alpha axis and d) a similar immune cell topography independently of the neoadjuvant chemotherapy. Conclusion: This study reveals the existence of dysfunctional T lymphocytes with specific spatial distribution, thus opening a new dimension both conceptually and mechanistically in tumor-stroma interaction in PDAC with potential impact on the efficacy of immune-regulatory therapeutic modalities. |
| Databáze: | OpenAIRE |
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