Tumor-associated macrophages (TAMs) account for approximately 50% of the tumor mass, and are inherently plastic cells that adopt two phenotypes, M1 and M2, with distinct functional states in response to environmental stimuli. This inherent plasticity of macrophages which allows for reprogramming to skew the M2/M1 ratio to the desired M1 phenotype, has emerged as a promising strategy for cancer immunotherapy. Although several recent studies have shown somewhat positive results on decreasing tumor progression in animal models after re-educating macrophages to the antitumorigenic M1 phenotype, the repolarized M1 macrophages could belatedly return to the M2 macrophages, thus losing sustained immune responses and showing limited anticancer efficacies.

Prof. DengHongzhang from School of Life Science and Technology, Xidian University,and his group have been working on establishing an X-ray guided and triggered remote control of a CRISPR/Cas9 genome editing system (X-CC9). The related paper has been published in the journal of ADVANCED MATERIALS (IF=32.086) lately. Under X-ray irradiation, X-CC9 selectively enhanced M2-to-M1 repolarization within the tumor microenvironment, and significantly improved anti-tumor efficacy with robust immune responses in two animal models. This strategy provides an ideal method for improving the safety of the macrophage polarization and may constitute a promising immunotherapy strategy.

Original article link:https://doi.org/10.1002/adma.202208059