PLX163308

GSE152925: Inhibition of MAN2A1 enhances tumor response to anti-PD-L1

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Immune checkpoint blockade (ICB) has shown remarkable efficacy, but in only a minority of cancer patients, suggesting the need to develop additional treatment strategies.We integrated transcriptional profiles of treatment-nave human tumors and functional CRISPR screens to identify glycometabolism genes with immunomodulatory effects. We identified MAN2A1, encoding an enzyme in N-glycan maturation, as a key immunomodulatory gene. Analyses of public immune checkpoint blockade trial data also suggested a synergy between MAN2A1 inhibition and anti-PD-L1 treatment. Loss of Man2a1 in cancer cells increased their sensitivity to T cell-mediated killing. Man2a1 knockout enhanced response to anti-PD-L1 treatment and facilitated higher cytotoxic T cell infiltration in tumors under anti-PD-L1 treatment. Furthermore, a pharmacological inhibitor of MAN2A1, swainsonine, synergized with anti-PD-L1 in syngeneic melanoma tumor model, whereas each treatment alone had little effect. SOURCE: jun ge (junge960214@gmail.com) - Tongji University