High-Lactate-Metabolizing Photosynthetic Bacteria Reprogram Tumor Immune Microenvironment.

Abstract

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency.