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Kerdidani, D.* ; Chouvardas, P.* ; Arjo, A.R.* ; Giopanou, I.* ; Ntaliarda, G.* ; Guo, Y.A.* ; Tsikitis, M.* ; Kazamias, G.* ; Potaris, K.* ; Stathopoulos, G.T. ; Zakynthinos, S.* ; Kalomenidis, I.* ; Soumelis, V.* ; Kollias, G.* ; Tsoumakidou, M.*

Wnt1 silences chemokine genes in dendritic cells and induces adaptive immune resistance in lung adenocarcinoma.

Nat. Commun. 10:1405 (2019)
Publ. Version/Full Text Research data DOI
Open Access Gold
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Lung adenocarcinoma (LUAD)-derived Wnts increase cancer cell proliferative/stemness potential, but whether they impact the immune microenvironment is unknown. Here we show that LUAD cells use paracrine Wnt1 signaling to induce immune resistance. In TCGA, Wnt1 correlates strongly with tolerogenic genes. In another LUAD cohort, Wnt1 inversely associates with T cell abundance. Altering Wnt1 expression profoundly affects growth of murine lung adenocarcinomas and this is dependent on conventional dendritic cells (cDCs) and T cells. Mechanistically, Wnt1 leads to transcriptional silencing of CC/CXC chemokines in cDCs, T cell exclusion and cross-tolerance. Wnt-target genes are up-regulated in human intratumoral cDCs and decrease upon silencing Wnt1, accompanied by enhanced T cell cytotoxicity. siWnt1-nanoparticles given as single therapy or part of combinatorial immunotherapies act at both arms of the cancer-immune ecosystem to halt tumor growth. Collectively, our studies show that Wnt1 induces immunologically cold tumors through cDCs and highlight its immunotherapeutic targeting.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Beta-catenin; C/ebp-beta; Expression; Progression; Responses; Dysregulation; Activation; Contexture; Prognosis; Pathways
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 1405 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed