Systemic injection of TLR1/2 agonist improves adoptive antigen-specific T cell therapy in glioma-bearing mice

• TLR1/2 agonist, BLP, enhances anti-glioma efficiency of adoptive T cell therapy.
• BLP maintains T cell survival and anti-glioma immunity in the brain.
• MDSC accumulation is decreased in the brain after combined therapy.
• The blockage of BLP by TLR2 deficiency greatly abrogates therapeutic effect.

Adoptive immunotherapy is an attractive strategy for glioma treatment. However, some obstacles still need be overcome. In this study, GL261-bearing mice treated with adoptively transferred antigen-specific T cells and systemic injection of bacterial lipoprotein (BLP), a TLR1/2 agonist, got a long-term survival and even immune protection. By analyzing adoptive T cells, it was found that BLP maintained T cell survival, proliferation and anti-tumor efficacy in the brains of tumor-bearing hosts. Moreover, tumor microenvironment was modified by up-regulating IFN-γ-secreting CD8+ T cells and down-regulating MDSC, which might be related with high CXCL10 and low CCL2 expression. In addition, TLR2 deficiency abrogated therapeutic effect with increased MDSC accumulation and decreased IFN-γ-secreting CD8+ T cells in the brains. Thus, the systemic injection of BLP could improve the adoptive T cell therapy by maintaining T cell persistence, modifying the tumor microenvironment and even inducing systemic anti-tumor immunity, which might offer a clinically promising immunotherapeutic strategy for glioma.