Β-Catenin inhibition shapes tumor immunity and synergizes with immunotherapy in colorectal cancer. (1st January 2020)

• Record Type: Journal Article
• Authors: Wang, Caihong; Yan, Jingjing; Yin, Pan; Gui, Liming; Ji, Lu; Ma, Bin; Gao, Wei-Qiang
• Is Part Of: Oncoimmunology. Volume 9:Number 1(2020)
• Publication Date: 2020-01-01
• Subjects: Wnt -- β-catenin -- tumor microenvironment -- immunotherapy -- colorectal cancer -- CXCR3 chemokine; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2020.1809947
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: In colorectal cancer, Wnt/β-catenin signaling is often aberrantly activated and associated with a T-cell-excluded phenotype which is a major obstacle for many immunotherapies. However, the effects of Wnt/β-catenin inhibition on tumor immunity and immunotherapy remain to be elucidated. In syngeneic mouse models of colorectal cancer, β-catenin/TCF inhibitor iCRT14 potently enhanced the infiltration of T and NK cells, without influencing their proliferation or the infiltration of most myeloid populations. Mechanistically, β-catenin inhibition upregulated while its overexpression suppressed the expression of T/NK cell-recruiting CXCR3 chemokines CXCL9/10/11 in both mouse and human colorectal cancer cells. Furthermore, iCRT14 treatment synergized with tumor vaccines or Treg cell ablation to achieve a complete inhibition of tumor growth in syngeneic models of CT26-OVA and MC38-S33Y.β-cat, respectively. Taken together, our work reveals that β-catenin inhibition shifts colorectal tumor microenvironment into a T-cell-inflamed phenotype and potentiates the efficacy of other immunotherapeutic strategies for colorectal cancer.