Potential role of intratumor bacteria outside the gastrointestinal tract: More than passengers

Abstract

Introduction: Tumor-associated bacteria and gut microbiota have gained significant attention in recent years due to their potential role in cancer development and therapeutic response. This review aims to discuss the contributions of intratumor bacteria outside the gastrointestinal tract, in addition to exploring the mechanisms, functions, and implications of these bacteria in cancer therapy.

Methods: We reviewed current literature on intratumor bacteria and their impact on tumorigenesis, progression, metastasis, drug resistance, and anti-tumor immune modulation. Additionally, we examined techniques used to detect intratumor bacteria, precautions necessary when handling low microbial biomass tumor samples, and the recent progress in bacterial manipulation for tumor treatment.

Results: Research indicates that each type of cancer uniquely interacts with its microbiome, and bacteria can be detected even in non-gastrointestinal tumors with low bacterial abundance. Intracellular bacteria have the potential to regulate tumor cells' biological behavior and contribute to critical aspects of tumor development. Furthermore, bacterial-based anti-tumor therapies have shown promising results in cancer treatment.

Conclusions: Understanding the complex interactions between intratumor bacteria and tumor cells could lead to the development of more precise cancer treatment strategies. Further research into non-gastrointestinal tumor-associated bacteria is needed to identify new therapeutic approaches and expand our knowledge of the microbiota's role in cancer biology.

Keywords: bacterial-mediated cancer therapy; carcinogenesis; intracellular bacteria; intratumor bacteria; tumor microenvironment.

FIGURE 1

Flowchart of common techniques for detecting and identifying intratumor bacteria, including FISH, IHC, and NGS, as well as the minimum recommended control set‐up to ensure experiment accuracy and reproducibility.

FIGURE 2

Four possible origins of bacteria in tumors outside the gastrointestinal tract: (i) Migration or invasion from the gastrointestinal tract; (ii) transfer from the circulatory system; (iii) transfer from the cardiovascular system; (iv) carried through a metastatic process by circulating tumor cells.

FIGURE 3

Three stages of tumor metastasis are facilitated by intracellular bacteria: (i) invasion and migration, (ii) maintenance of circulating tumor cell survival, and (iii) targeted colonization of tumor cells. Both in the primary tumor and in the metastases, intratumor bacteria are crucial to the metastatic process.