共激活 TLR 与 STING 信号通路工程化炎性巨噬细胞的瘤内过继转移及其强效抗肿瘤活性

Despite the success of chimeric antigen receptor (CAR) T cells in hematologic malignancies, adoptive cell therapy (ACT) has not been effective in treating solid tumors.

Here, we developed an inflammatory macrophage-based ACT to effectively treat solid tumors.

We engineered inflammatory macrophages to enhance their antitumor activities, including proinflammatory cytokine secretion and co-stimulatory molecule expression by co-activating toll-like receptor and stimulator of interferon genes signaling pathways.

Engineered macrophages maintain an inflammatory phenotype after their adoptive transfer into the anti-inflammatory tumor microenvironment (TME), whereas conventional inflammatory macrophages prepared using interferon- treatment are repolarized to an anti-inflammatory phenotype. In a mouse melanoma model, intratumoral adoptive transfer of engineered macrophages showed robust tumor growth inhibition by increasing CD8 + T cells in the TME and tumor antigen-specific CD8 + T cells in the blood.

This study demonstrated that engineered inflammatory macrophages have potential as an effective ACT for treating solid tumors.