SHISA3 Reprograms Tumor‐Associated Macrophages Toward an Antitumoral Phenotype and Enhances Cancer Immunotherapy

Author:

Zhang Shimeng1,Yu Bingbing2,Sheng Chunjie1,Yao Chen1,Liu Yang1,Wang Jing1,Zeng Qi1,Mao Yizhi1,Bei Jinxin1,Zhu Bin23,Chen Shuai1ORCID

Affiliation:

1. State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐sen University Cancer Center Guangzhou 510060 P. R. China

2. Key Laboratory of Molecular Biophysics the Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Wuhan Hubei 430074 P. R. China

3. Shenzhen Huazhong University of Science and Technology Research Institute Shenzhen 518063 P. R. China

Abstract

AbstractThe main challenge for immune checkpoint blockade (ICB) therapy lies in immunosuppressive tumor microenvironment (TME). Repolarizing M2‐like tumor‐associated macrophages (TAMs) into inflammatory M1 phenotype is a promising strategy for cancer immunotherapy. Here, this study shows that the tumor suppressive protein SHISA3 regulates the antitumor functions of TAMs. Local delivery of mRNA encoding Shisa3 enables cancer immunotherapy by reprogramming TAMs toward an antitumoral phenotype, thus enhancing the efficacy of programmed cell death 1 (PD‐1) antibody. Enforced expression of Shisa3 in TAMs increases their phagocytosis and antigen presentation abilities and promotes CD8+ T cell‐mediated antitumor immunity. The expression of SHISA3 is induced by damage/pathogen‐associated molecular patterns (DAMPs/PAMPs) in macrophages via nuclear factor‐κB (NF‐κB) transcription factors. Reciprocally, SHISA3 forms a complex with heat shock protein family A member 8 (HSPA8) to activate NF‐κB signaling thus maintaining M1 polarization of macrophages. Knockout Shisa3 largely abolishes the antitumor efficacy of combination immunotherapy with Toll‐like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) and PD‐1 antibody. It further found that higher expression of SHISA3 in antitumoral TAMs is associated with better overall survival in lung cancer patients. Taken together, the findings describe the role of SHISA3 in reprogramming TAMs that ameliorate cancer immunotherapy.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3