Bacterial-Mediated In Situ Engineering of Tumour-Associated Macrophages for Cancer Immunotherapy.

Background/objectives: Tumour-associated macrophages (TAMs) are critical components of the tumour microenvironment (TME), significantly influencing cancer progression and treatment resistance. This review aims to explore the innovative use of engineered bacteria to reprogram TAMs, enhancing their anti-tumour functions and improving therapeutic outcomes.

Methods: We conducted a systematic review following a predefined protocol. Multiple databases were searched to identify relevant studies on TAMs, their phenotypic plasticity, and the use of engineered bacteria for reprogramming. Inclusion and exclusion criteria were applied to select studies, and data were extracted using standardised forms. Data synthesis was performed to summarise the findings, focusing on the mechanisms and therapeutic benefits of using non-pathogenic bacteria to modify TAMs.

Results: The review summarises the findings that engineered bacteria can selectively target TAMs, promoting a shift from the tumour-promoting M2 phenotype to the tumour-fighting M1 phenotype. This reprogramming enhances pro-inflammatory responses and anti-tumour activity within the TME. Evidence from various studies indicates significant tumour regression and improved immune responses following bacterial therapy.

Conclusions: Reprogramming TAMs using engineered bacteria presents a promising strategy for cancer therapy. This approach leverages the natural targeting abilities of bacteria to modify TAMs directly within the tumour, potentially improving patient outcomes and offering new insights into immune-based cancer treatments. Further research is needed to optimise these methods and assess their clinical applicability.