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Highly immunogenic cancer cells require activation of the WNT pathway for immunological escape

Yoshiko Takeuchi, Tokiyoshi Tanegashima, Eiichi Sato, Takuma Irie, Atsuo Sai, Kota Itahashi, Shogo Kumagai, Yasuko Tada, Yosuke Togashi, Shohei Koyama, Esra A. Akbay, Takahiro Karasaki, Keisuke Kataoka, Soichiro Funaki, Yasushi Shintani, Izumi Nagatomo, Hiroshi Kida, Genichiro Ishii, Tomohiro Miyoshi, Keiju Aokage, Kazuhiro Kakimi, Seishi Ogawa, Meinoshin Okumura, Masatoshi Eto, Atsushi Kumanogoh, Masahiro Tsuboi, Hiroyoshi Nishikawa

2021Science Immunology131 citationsDOI

Abstract

T cells from tumors in a WNT/β-catenin signaling-dependent manner. Combined treatment with PD-1 blockade and WNT/β-catenin signaling inhibitors induced better antitumor immunity than either treatment alone. Thus, we propose a mechanism-oriented combination therapy whereby immune checkpoint inhibitors can be combined with drugs that target cell-intrinsic oncogenic signaling pathways involved in tumor immune escape.

Topics & Concepts

Wnt signaling pathwayCancer researchTumor microenvironmentCD8Immune systemBiologyT cellCytotoxic T cellImmunologyImmune checkpointSignal transductionImmunotherapyCell biologyIn vitroBiochemistryCancer Immunotherapy and BiomarkersImmunotherapy and Immune ResponsesImmune Cell Function and Interaction
Highly immunogenic cancer cells require activation of the WNT pathway for immunological escape | Litcius