Fig. 7: Treg depletion amplifies the effectiveness of vaccines targeting tumor-associated antigens.
From: Regulatory T cells define affinity thresholds for CD8+ T cell tumor infiltration
A A cartoon illustrating the generated multitarget vaccine (MTV) consisting of six CD8+ T-cell germline epitopes of B16F10 melanoma cells that were identified using immunopeptidomics and whole exome sequencing. The length distribution of the selected peptides was 8 and 9 amino acids17. B SDS-PAGE stained with Coomassie Blue, with Lane 1, protein marker; Lane 2, Qβ(CpGs) at 14 kDa; and Lane 3, Qβ(CpGs) derivatized with a dibenzocyclooctyne bifunctional cross-linker (DBCO), Lanes 4–9 show coupling to TAAs peptides: PMEL (VLYRYGSF), MTC-1 (IGIENIHYL), Calpastatin (SSPANISSL), Zinc-finger protein 518B (SSVQNKEYL), Tyrosinase-related protein 2 (SQVMNLHNL) and Caveolin2 (VMYKFLTV) respectively. Red box indicates Qβ(CpGs) monomer before and after derivatization with DBCO and coupling to peptides. Black arrows indicate the coupled peptides to the Qβ monomer. C An illustration depicting the vaccination regimen with MTV administered following transplantation of B16F10p33 tumors, combined with intravenous injection of anti-CD25 mAb for effective depletion of Tregs. Four experimental groups were established: Qβ (control), a group vaccinated with MTV alone, a group receiving MTV vaccination combined with Treg depletion (MTV/Treg depl), and a Treg depletion control group. D Tumor volume mm3. E Tumor volume mm3 of individual mice. F Density of CD8+ T cells in the tumors. G Representative flow cytometry plots illustrating the total number of CD8+ T cells acquired from a tumor in each group. H Density of IFN-γ producing CD8+ T cells in the tumor. Stimulation was conducted using a mixture of peptides. Statistical analysis with Student’s t-test. The sample size for each group was n = 5.
