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Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused CD47-SIRP proportional to Expression
Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
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2020 (English)In: Cancers, ISSN 2072-6694, Vol. 12, no 7, article id 1825Article in journal (Refereed) Published
Abstract [en]

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 a 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.

Place, publisher, year, edition, pages
2020. Vol. 12, no 7, article id 1825
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-174629DOI: 10.3390/cancers12071825ISI: 000557225400001Scopus ID: 2-s2.0-85090734510OAI: oai:DiVA.org:umu-174629DiVA, id: diva2:1462684
Available from: 2020-08-31 Created: 2020-08-31 Last updated: 2023-03-24Bibliographically approved

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Bergonzini, AnnaFrisan, Teresa

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Chiloeches, mariaBergonzini, AnnaFrisan, Teresa
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