HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing-Reference-Cited by-同舟云学术

HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing

Published:2024-06-07 Issue:23 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Wu Hong¹²³⁴^ORCID,Liu Yiqiang¹²³⁴^ORCID,Liu Qianshi¹²³⁴^ORCID,Li Zhaoshen¹²³⁴^ORCID,Wan Yejian¹²³⁴^ORCID,Cao Chenhui¹²³⁴^ORCID,Wu Binghuo¹²³⁴^ORCID,Liu MingXin¹²³⁴^ORCID,Liang Renchuan¹²³⁴^ORCID,Hu Lanlin¹²³⁴^ORCID,Zhang Wenyi¹²³⁴^ORCID,Lan Mei⁵^ORCID,Yao Quan⁵^ORCID,Zhou Hang⁵^ORCID,Lan Haitao¹²^ORCID,Chen Liang⁶^ORCID,Zhang Yu⁷^ORCID,Zhang Xia³^ORCID,Bian Xiu-Wu³⁴⁸^ORCID,Xu Chuan¹²³⁴⁸^ORCID

Affiliation:

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.

5. Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, P. R. China.

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.

8. Jinfeng Laboratory, Chongqing 400039, P. R. China.

Abstract

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. HMMR high liver cancer cells escaped from phagocytosis via sustaining CD47 signaling. Patients with HMMR high CD47 high expression showed a worse prognosis than those with HMMR low CD47 low 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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adl6083

Reference47 articles.

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3. Roles of macrophages in tumor development: a spatiotemporal perspective

4. CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells

5. SIRPγ-expressing cancer stem-like cells promote immune escape of lung cancer via Hippo signaling

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