| First Author | Wu H | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 23 | Pages | eadl6083 |
| PubMed ID | 38838151 | Mgi Jnum | J:349101 |
| Mgi Id | MGI:7646500 | Doi | 10.1126/sciadv.adl6083 |
| Citation | Wu H, et al. (2024) HMMR triggers immune evasion of hepatocellular carcinoma by inactivation of phagocyte killing. Sci Adv 10(23):eadl6083 |
| abstractText | 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-kappaB 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. |
