机构：[1]Department of Oncology &Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.四川省人民医院[2]Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.四川省人民医院[3]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P. R. China.[4]Yu-Yue Pathology Scientific Research Center, Chongqing 400039, P. R. China.[5]Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.四川省肿瘤医院[6]Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei 230027, P. R. China.[7]The Department of Hepatobiliary and Pancreatic Surgery, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.四川省人民医院[8]Jinfeng Laboratory, Chongqing 400039, P. R. China.
Hepatocellular carcinoma (HCC) acquires an immunosuppressive microenvironment, leading to unbeneficial therapeutic outcomes. Hyaluronan-mediated motility receptor (HMMR) plays a crucial role in tumor progression. Here, we found that aberrant expression of HMMR could be a predictive biomarker for the immune suppressive microenvironment of HCC, but the mechanism remains unclear. We established an HMMR-/- liver cancer mouse model to elucidate the HMMR-mediated mechanism of the dysregulated "don't eat me" signal. HMMR knockout inhibited liver cancer growth and induced phagocytosis. HMMRhigh liver cancer cells escaped from phagocytosis via sustaining CD47 signaling. Patients with HMMRhighCD47high expression showed a worse prognosis than those with HMMRlowCD47low expression. HMMR formed a complex with FAK/SRC in the cytoplasm to activate NF-κB signaling, which could be independent of membrane interaction with CD44. Notably, targeting HMMR could enhance anti-PD-1 treatment efficiency by recruiting CD8+ T cells. Overall, our data revealed a regulatory mechanism of the "don't eat me" signal and knockdown of HMMR for enhancing anti-PD-1 treatment.
基金：
This work was supported by the National Key Research and
Development Program of China Stem Cell and Translational Research (2023YFC3402100) and
the National Natural Science Foundation of China (92259102, 82372597, and 81873048).
第一作者机构：[1]Department of Oncology &Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.[2]Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.[3]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P. R. China.[4]Yu-Yue Pathology Scientific Research Center, Chongqing 400039, P. R. China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Oncology &Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.[2]Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.[3]Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, P. R. China.[4]Yu-Yue Pathology Scientific Research Center, Chongqing 400039, P. R. China.[8]Jinfeng Laboratory, Chongqing 400039, P. R. China.
推荐引用方式(GB/T 7714)：
Wu Hong,Liu Yiqiang,Liu Qianshi,et al.HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing[J].SCIENCE ADVANCES.2024,10(23):eadl6083.doi:10.1126/sciadv.adl6083.
APA：
Wu Hong,Liu Yiqiang,Liu Qianshi,Li Zhaoshen,Wan Yejian...&Xu Chuan.(2024).HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing.SCIENCE ADVANCES,10,(23)
MLA：
Wu Hong,et al."HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing".SCIENCE ADVANCES 10..23(2024):eadl6083
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