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LAG-3-Expressing Tumor-Infiltrating T Cells Are Associated with Reduced Disease-Free Survival in Pancreatic Cancer

Authors: 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.

Online: https://www.mdpi.com/2072-6694/13/6/1297

Issue: Cancers (Basel) . 2021 Mar 15;13(6):1297.


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.