# Targeting the LPS-STING axis: neomycin restores STING-mediated anti-tumor immune suppression and inhibits tumor growth

## TL;DR

This study shows that LPS from bacteria in tumors suppresses immune responses, and using neomycin with STING agonists can help fight cancer.

## Contribution

The study reveals a novel therapeutic strategy combining neomycin and STING agonists to enhance anti-tumor immunity.

## Key findings

- Low-dose LPS pretreatment suppressed IFN-β secretion by macrophages, indicating immunosuppression.
- Neomycin treatment inhibited melanoma growth and synergized with STING agonists in mice.
- LPS in the tumor microenvironment impairs macrophage function and anti-tumor immunity.

## Abstract

The interplay between microbial metabolites and host immunity within the tumor microenvironment (TME) critically modulates anti-tumor immune responses. The role of Gram-negative bacteria and their cell wall component lipopolysaccharide (LPS) in this context warrants further investigation.

We assessed the impact of low-dose LPS pretreatment on macrophage function by measuring type I interferon (IFN-β) secretion in response to tumor cell debris. Mechanistic insights were gained by analyzing endogenous signaling pathways in macrophages. The therapeutic potential of targeting LPS was evaluated in melanoma-bearing mice treated with neomycin, alone or in combination with STING agonists.

Low-dose LPS pretreatment significantly suppressed IFN-β secretion by macrophages, indicating LPS-mediated immunosuppression. Mechanistically, LPS disrupted endogenous signaling pathways, blunting the ability of macrophages to sense tumor-derived damage signals. In vivo, neomycin treatment markedly inhibited melanoma growth and synergized with STING agonists.

Our findings demonstrate that elevated LPS in the TME inhibits anti-tumor innate immunity by impairing macrophage function. The combination of LPS modulation via neomycin with innate immune activation via STING agonists presents a potential strategy to enhance tumor immunotherapy.