What question did this study set out to answer?

The aim is to explore a bacteria-mimetic strategy for reprogramming macrophages to enhance their antitumor responses.

February 21, 2026

BPS2026 – Reprogramming macrophages with bacteria-mimetic cancer cells for potent innate antitumor responses

Key Points

The aim is to explore a bacteria-mimetic strategy for reprogramming macrophages to enhance their antitumor responses.
Engineered tumor cell membranes to display pathogen-associated molecular patterns (PAMPs)
Co-cultured PAMP-decorated cancer cells with macrophages
Evaluated phagocytic activity and cytokine secretion
Performed transcriptomic profiling for innate immune activation
In vivo injections of PAMP-coated nanoparticles in tumor-bearing mice, with and without doxorubicin.
Phagocytosis activity nearly doubled in macrophages exposed to PAMP-decorated cancer cells
Significant increase in TNF-α and IL-6 secretion compared to control
Transcriptomic analysis showed upregulation of Toll-like receptor and NF-κB signaling pathways
Intratumoral administration of nanoparticles suppressed tumor growth
Doxorubicin co-treatment enhanced tumor regression beyond single therapies.

Abstract

Macrophages are critical regulators of innate immunity and have emerged as a promising target in cancer immunotherapy. However, the tumor microenvironment often suppresses their antitumor functions, which include phagocytosis and pro-inflammatory cytokine release. Here, we present a bacteria-mimetic strategy to reactivate macrophages by engineering tumor cell membranes to display pathogen-associated molecular patterns (PAMPs). To generate this effect, we decorated cancer cell membranes with PAMP-carrying nanoparticles and co-cultured them with macrophages. We quantified phagocytic activity and cytokine secretion and performed transcriptomic profiling to evaluate innate immune activation. In vivo, PAMP-coated nanoparticles were injected into tumor-bearing mice alone or with doxorubicin to evaluate therapeutic efficacy. Macrophages exposed to PAMP-decorated cancer cells exhibited robust reprogramming. Phagocytosis nearly doubled, and secretion of TNF-α and IL-6 significantly increased compared to controls. Transcriptomic analysis revealed the upregulation of Toll-like receptor and NF-κB signaling pathways, which is consistent with the activation seen in bacterial infections. Intratumoral administration of PAMP-coated nanoparticles strongly suppressed tumor growth in vivo. Notably, co-treatment with doxorubicin further potentiated tumor regression, surpassing the effects of either therapy alone. Histological analysis demonstrated enhanced macrophage infiltration and apoptotic tumor cell death. This study establishes that mimicking a bacterial infection by using surface-engineered cancer cells can effectively overcome tumor-induced immunosuppression. By reactivating macrophages, this approach provides a powerful means to harness innate immunity against cancer. Furthermore, its synergy with chemotherapy highlights its potential for combinatorial therapeutic strategies in clinical applications. Our findings pave the way for a new approach to biophysically inspired immunotherapy, in which engineered membrane interfaces can reprogram innate immune cells to restore their natural tumor-clearing functions.

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