HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38838151.
- Also identified by DOI 10.1126/sciadv.adl6083 and PMC identifier 11152120.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-/-</sup> 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<sup>high</sup> liver cancer cells escaped from phagocytosis via sustaining CD47 signaling. Patients with HMMR<sup>high</sup>CD47<sup>high</sup> expression showed a worse prognosis than those with HMMR<sup>low</sup>CD47<sup>low</sup> 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<sup>+</sup> 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.
Medical subject headings
- Carcinoma, Hepatocellular
- CD47 Antigen
- Hyaluronan Receptors
- Liver Neoplasms
- Phagocytes
- Phagocytosis