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Media type:
E-Article
Title:
LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer
Contributor:
Seifert, Lena;
Plesca, Ioana;
Müller, Luise;
Sommer, Ulrich;
Heiduk, Max;
von Renesse, Janusz;
Digomann, David;
Glück, Jessica;
Klimova, Anna;
Weitz, Jürgen;
Schmitz, Marc;
Seifert, Adrian M.
Published:
MDPI AG, 2021
Published in:
Cancers, 13 (2021) 6, Seite 1297
Language:
English
DOI:
10.3390/cancers13061297
ISSN:
2072-6694
Origination:
Footnote:
Description:
<jats:p>T cells are the predominant immune cell population in the pancreatic tumor microenvironment. High CD8+ and Th1-polarized CD4+ T cell infiltration is associated with prolonged survival in human pancreatic ductal adenocarcinoma (PDAC). However, the expression pattern of co-stimulatory and inhibitory receptors by PDAC-infiltrating T cells and their prognostic significance are not well defined. In this study, we employed multiplex immunofluorescence to investigate the intratumoral expression of the co-stimulatory receptor inducible T-cell co-stimulator (ICOS), the inhibitory receptors lymphocyte-activation gene 3 (LAG-3), programmed death 1 (PD-1), and V-domain immunoglobulin suppressor of T cell activation (VISTA) by tumor-infiltrating T cells (CD3) in a cohort of 69 patients with resected PDAC. T cells were enriched particularly within the stromal area and were highly heterogeneous across tumors. Further, T cells were associated with prolonged disease-free survival (DFS). However, LAG-3 expression by PDAC-infiltrating T cells was correlated with reduced DFS. Our study highlights the biological importance of LAG-3 expression by tumor-infiltrating T cells. LAG-3+ T cells may represent a novel prognostic marker and a particularly attractive target for immunotherapeutic strategies in PDAC.</jats:p>