In Situ Colonization of Trojan‐Yeast for Targeted Glucose Starvation and Reconstruction of Tumor Immune Environment

Abstract Glucose is an important energy source for living cells. Particularly, most tumor cells use glycolysis to harness energy for their fast growth, invasion and metastasis even under aerobic conditions. Thus, reduction of the glucose level in cancer can lead to suppression of tumor growth. Here, macrophage membrane dressed yeast, Trojan M‐yeast, is developed, via coating the surface of yeast with macrophage membrane, for targeted accumulation and suppression of tumor by glucose starvation. Due to the inflammatory homing effects of macrophage membrane, M‐yeast efficiently target and colonize in the inflammatory tumor site, where they compete with tumor cells for glucose consumption, thereby disrupting glycolysis of cancer cells, resulting in the reduction of lactate accumulation and reversal of the acidosis of tumor microenvironment. Subsequently, the apoptotic tumor cells and yeast promote dendritic cell maturation, increase tumor‐infiltrating cytotoxic T lymphocytes. Meanwhile, ethanol and acetaldehyde produced by yeast metabolism of glucose can re‐polarize tumor associated macrophages (TAMs) to the anti‐tumor phenotype (M1), thus reprogramming the tumor immunosuppressive microenvironment, leading to synergistic tumor suppression together with glucose starvation, which is different from traditional chemotherapy and immunotherapy. M‐yeast exhibits promising targeted cancer therapy with a decent safety profile. This work may provide new insights as well as a new paradigm for yeast‐based cancer therapy.