Fig. 7: MET suppresses liver cancer vaccination through V-ATPase–MTOR signaling.
From: The AKT-independent MET–V-ATPase–MTOR axis suppresses liver cancer vaccination
a, b MTOR inhibition improves the protective efficacy of chemotherapy-based liver cancer vaccination. Wild-type (WT) H22 cells (a) and Hepa1-6 cells (b) were individually treated with rapamycin (RAPA) alone or in combination with cisplatin (CDDP) or oxaliplatin (OXP) and then subcutaneously (s.c.) injected into the left flank of C57BL/6 mice. One week later, all the mice were rechallenged with homologous untreated WT cells in the right flank. The tumor incidence is reported as Kaplan–Meier curves. Significance was determined by the means calculated with a likelihood ratio test. c, d MTOR activation suppresses MET deficiency-enhanced liver cancer immunogenicity. MET-deficient (MET-KO) H22 cells (c) and Hepa1-6 cells (d) were individually treated with 3BDO alone or in combination with CDDP or OXP, respectively, and subsequently experiments were conducted as previously described. e, f V-ATPase inhibition enhances the protective efficacy of chemotherapy-based liver cancer vaccination. WT H22 cells (e) and Hepa1-6 cells (f) were individually treated with concanamycin A (Con A) alone or in combination with CDDP or OXP, and then conducted as previously described. g, h Rag GTPase activation suppresses MET deficiency-enhanced liver cancer immunogenicity. MET-KO H22 cells (g) and Hepa1-6 cells (h) were individually transfected and treated with the RagB Q99L (RagBGTP) mutant alone or in combination with CDDP or OXP and subsequently conducted as before. *p-Value < 0.05, **p-value < 0.01, ***p-value < 0.001, ns (nonsignificant), compared to the indicated groups; n = 10 per group.
