Generally speaking, proteins embedded on the cell membrane randomly flow with the flow of membrane lipids, which is termed “fluid mosaic model”. With the emergence of lipid raft, we understand the cytoplasm membrane more deeply. Given the critical role of cytoplasm, what are the design ideas for lipid raft?

Today, let’s share a paper entitled “B3GALT4 remodels the tumor microenvironment through GD2-mediated lipid raft formation and the c-met/AKT/mTOR/IRF-1 axis in neuroblastoma” published on Journal of Experimental & Clinical Cancer Research (Chinese Academy of Sciences, Q1), with an IF of 11.3, hoping to provide inspirations.

1. Research background

l Whether gangliosides GD2 impacts lipid raft and relevant AKT and c-Met signaling pathway activation?

l B3GALT4 regulates the formation of lipid rafts via GD2, but the function and mechanism of neuroblastoma (NB) in the immunity remains unclear.

l Whether chemokines CXCL9 and CXCL10 in NB cells attract CD8+T lymphocytes to NB tumor tissues?

l Whether the combination of lipid raft inhibitor and anti-GD2 antibody can effectively enhance the efficacy of immunotherapy for NB?

2. Technical route

3. Research results

Ø GD2 was overexpressed in NB tissues and mediated by B3GALT4.

Ø B3GALT4 expression was down-regulated in NB tissues, indicating a poor prognosis.

Ø B3GALT4 overexpression can block the progression of NB in vivo and in vitro.

Ø B3GALT4 overexpression induced CD8+T-cell infiltration mediated by CXCL9 and CXCL10.

Ø B3GALT4 mediated lipid raft formation via GD2.

Ø B3GALT4 regulated CXCL9 and CXCL10 expressions by cmet signaling in the lipid rafts and the downstream AKT/mTOR/IRF-1 pathway.

Ø The lipid raft inhibitor MβCD suppressed B3GALT4 knockdown-mediated tumor progression and immune escape.

Ø Anti-GD2 immunotherapy combined with MβCD promoted CD8+T-cell infiltration via CXCL9 and CXCL10.

4. Conclusion

Based on database analyses and experimental data, this study demonstrates the influences of B3GALT4 on NB progression and the relation between B3GALT4 and lipid raft formation, that is, B3GALT4 regulates lipid raft formation through GD2, during which the role of lipid raft-related pathways has also been verified. Ultimately, the foundation of the regulatory mechanism is further potentiated with the rescuing effect of lipid raft inhibitor. According to the practical application, the combination of anti-GD2 immunotherapy and MβCD can further enhance the therapeutic efficacy in NB mice.