Abstract Intratumoral bacteria play vital roles in regulating tumor progression by stimulating pro‐inflammatory signals or modulating the tumor microenvironment. Due to distinct characteristics, such as intrinsic targeting of tumors or inherent immunogenicity, intratumoral bacteria are capable of inducing specific tumor cell apoptosis and necrosis, or even reprogramming the tumor immune microenvironment by interacting with the immune system. Such efficacy can be further enhanced by the modifications and engineering processes, which may efficiently inhibit tumor growth with minimal side effects, thus demonstrating promising clinical translation potential. Therefore, in this review, the development and characteristics of intratumoral bacteria and their impact on tumor progression are described in detail. Moreover, the strategies and applications of these intratumoral bacteria, which are explicitly engineered to induce tumor regression through direct killing or immune modulation, are also included. Additionally, the mechanisms by which these engineered intratumoral bacteria regulate tumor progression are elucidated and discussed. More importantly, the translational significance, current challenges in clinical adaptation, and possible solutions to these challenges of engineered intratumoral bacteria are also highlighted. Overall, this comprehensive review may provide perspectives regarding the intratumoral bacteria and may offer new insights for developing novel bacteria‐based therapeutic platforms against tumors.
Zhang et al. (Tue,) studied this question.