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    Unique spatial immune profiling in pancreatic ductal adenocarcinoma with enrichment of exhausted and senescent T cells and diffused CD47-SIRP? expression

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    Authors
    Papalampros, A.
    Vailas, M.
    Ntostoglou, K.
    Chiloeches, M. L.
    Sakellariou, S.
    Chouliari, N. V.
    Samaras, M. G.
    Veltsista, P. D.
    Theodorou, S. D. P.
    Margetis, A. T.
    Bergonzini, A.
    Karydakis, L.
    Hasemaki, N.
    Havaki, S.
    Moustakas, II
    Chatzigeorgiou, A.
    Karamitros, T.
    Patsea, E.
    Kittas, C.
    Lazaris, A. C.
    Felekouras, E.
    Gorgoulis, Vassilis G
    Frisan, T.
    Pateras, I. S.
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    Affiliation
    First Department of Surgery, Laikon University Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece
    Issue Date
    2020
    
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    Abstract
    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? 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. Keywords: CD47; T cell exhaustion; T cell senescence; draining lymph nodes; macrophage checkpoint; neoadjuvant chemotherapy; pancreatic ductal adenocarcinoma; signal regulatory protein alpha (SIRP?); spatial heterogeneity; tumor microenvironment.
    Citation
    Papalampros A, Vailas M, Ntostoglou K, Chiloeches ML, Sakellariou S, Chouliari NV, et al. Unique Spatial Immune Profiling in Pancreatic Ductal Adenocarcinoma with Enrichment of Exhausted and Senescent T Cells and Diffused CD47-SIRPalpha Expression. Cancers (Basel). 2020;12(7).
    Journal
    Cancers
    URI
    http://hdl.handle.net/10541/623176
    DOI
    10.3390/cancers12071825
    PubMed ID
    32645996
    Additional Links
    https://dx.doi.org/10.3390/cancers12071825
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers12071825
    Scopus Count
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