Wnt/β-Catenin Signaling and Resistance to Immune Checkpoint Inhibitors: From Non-Small-Cell Lung Cancer to Other Cancers.

Content Provider	Europe PMC
Author	Muto, Satoshi Enta, Akio Maruya, Yoshiyuki Inomata, Sho Yamaguchi, Hikaru Mine, Hayato Takagi, Hironori Ozaki, Yuki Watanabe, Masayuki Inoue, Takuya Yamaura, Takumi Fukuhara, Mitsuro Okabe, Naoyuki Matsumura, Yuki Hasegawa, Takeo Osugi, Jun Hoshino, Mika Higuchi, Mitsunori Shio, Yutaka Hamada, Kazuyuki Suzuki, Hiroyuki
Editor	Wada, Satoshi
Copyright Year	2023
Abstract	Lung cancer is the leading cause of cancer-related deaths worldwide. The standard of care for advanced non-small-cell lung cancer (NSCLC) without driver-gene mutations is a combination of an anti-PD-1/PD-L1 antibody and chemotherapy, or an anti-PD-1/PD-L1 antibody and an anti-CTLA-4 antibody with or without chemotherapy. Although there were fewer cases of disease progression in the early stages of combination treatment than with anti-PD-1/PD-L1 antibodies alone, only approximately half of the patients had a long-term response. Therefore, it is necessary to elucidate the mechanisms of resistance to immune checkpoint inhibitors. Recent reports of such mechanisms include reduced cancer-cell immunogenicity, loss of major histocompatibility complex, dysfunctional tumor-intrinsic interferon-γ signaling, and oncogenic signaling leading to immunoediting. Among these, the Wnt/β-catenin pathway is a notable potential mechanism of immune escape and resistance to immune checkpoint inhibitors. In this review, we will summarize findings on these resistance mechanisms in NSCLC and other cancers, focusing on Wnt/β-catenin signaling. First, we will review the molecular biology of Wnt/β-catenin signaling, then discuss how it can induce immunoediting and resistance to immune checkpoint inhibitors. We will also describe other various mechanisms of immune-checkpoint-inhibitor resistance. Finally, we will propose therapeutic approaches to overcome these mechanisms.
Journal	Biomedicines
Volume Number	11
PubMed Central reference number	PMC9855612
Issue Number	1
PubMed reference number	36672698
e-ISSN	22279059
DOI	10.3390/biomedicines11010190
Language	English
Publisher	MDPI
Publisher Date	2023-01-12
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	immune checkpoint inhibitors tumor escape immunomodulation tumor microenvironment beta catenin Wnt signaling pathway cancer immunotherapy non-small-cell lung cancer
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry, Genetics and Molecular Biology