Reprogramming Tumor-Associated Macrophages by Nanoparticle-Based Reactive Oxygen Species Photogeneration

Without
coordinated strategies to mitigate the immunosuppressive
nature of the tumor microenvironment, cancer immunotherapy generally
offers limited clinical benefit for established tumors. Tumor-associated
macrophages (TAMs) are the critical driver of this immunosuppressive
tumor microenvironment, which also promotes tumor metastasis. Here
we successfully reprogrammed TAMs to an antitumor M1 phenotype using
precision nanoparticle-based reactive oxygen species photogeneration,
which demonstrated superior efficiency and efficacy over lipopolysaccharide
stimulation. Meanwhile, antigen presentation and T-cell-priming by
TAMs were enhanced by inhibiting lysosomal proton pump and proteolytic
activity or by promoting tumor associated antigen release in the cytoplasm.
The reprogrammed TAMs orchestrate cytotoxic lymphocyte (CTL) recruitment
in the tumor and direct memory T-cells toward tumoricidal responses.
This strategy could effectively eradicate tumors, inhibit metastasis,
and further prevent their recurrence, which holds tremendous promise
to realize potent cancer immunotherapy.