The microbiome, a complex community of microorganisms including bacteria, viruses, and fungi, within tumors significantly impacts cancer progression. Recent studies have shown that fungi residing in tumors can enhance the effects of cancer-associated bacteria. For example, the fungus Malassezia in pancreatic tumors activates immune pathways that promote tumor growth, while Aspergillus sydowii exacerbates inflammation and accelerates tumor development in lung cancer.
The tumor microbiome also aids in predicting cancer progression and recurrence. Moreover, it influences treatment outcomes, such as the response to immune checkpoint inhibitors (ICI). Scientists from the State Key Laboratory of Oncology in Southern China have described how the tumor microbiome contributes to cancer progression and interacts with the immune system.
Genetic Material Alteration
Certain bacteria within tumors can promote cancer development by affecting DNA integrity:
- Campylobacter spp. may cause DNA breaks, increasing the risk of colorectal cancer. This DNA damage might occur by producing specific toxins, enzymes, and reactive oxygen species.
- Lactobacillus iners can alter DNA repair mechanisms, making cancer cells more resistant to treatment, especially in cervical cancer.
- Some bacteria, such as Fusobacterium nucleatum, activate long non-coding RNAs, leading to DNA alterations and promoting colorectal cancer by accelerating glycolysis, the process through which cells generate energy.
Impact on Signaling Pathways
Certain intratumoral bacteria interfere with signaling pathways that regulate cell growth, facilitating cancer progression:
- Fusobacterium nucleatum secretes the FadA protein, activating the Wnt/β-catenin signaling pathway crucial for cell growth and division. Disruption of this pathway can lead to colorectal cancer. Other bacteria, like Salmonella and Helicobacter pylori, also influence this pathway.
- Fusobacterium activates the NF-κB signaling pathway, accelerating tumor growth in the colon.
- Porphyromonas gingivalis, associated with gum disease, activates intestinal cells’ MAPK/ERK signaling pathway, promoting rapid cancer cell division.
Alteration of Anticancer Drug Metabolism
Intratumoral bacteria can reduce the effectiveness of anticancer drugs by modifying their action and helping tumors become resistant to chemotherapy:
- Gammaproteobacteria metabolize the gemcitabine, converting it into an inactive form and reducing its effectiveness in treating pancreatic cancer.
- Escherichia coli reduces the toxicity of 5-fluorouracil by altering its structure. This drug is used in colorectal cancer treatment.
- Fusobacterium nucleatum enhances cancer cell resistance to 5-fluorouracil by affecting signaling pathways, regulating cell death, and reducing responsiveness to chemotherapy.
Immune Regulation
The immune system plays a crucial role in combating cancer. Bacteria within tumors can modulate the activity of immune cells:
- Ruminococcus gnavus and Blautia producta assist CD8 T-cells in controlling colorectal cancer development.
- Lactobacillus reuteri can travel through the body and activate immune cells in distant intestinal tumors like melanomas. These bacteria secrete substances that stimulate CD8 T-cells to produce interferon-γ, aiding in cancer immunotherapy.
Some bacterial compounds can enhance immune responses in breast cancer, helping immune cells target the tumor. Studies suggest that bacterial polypeptides may mimic cancer antigens, molecules that trigger an immune response, thereby boosting the immune system’s ability to fight cancer.
Metastasis
The primary cause of cancer-related mortality is metastasis, the spread of cancer cells throughout the body, and the formation of new tumor sites. The tumor microbiome can contribute to metastasis:
- E. coli in colorectal cancer tissues can disrupt the intestinal vascular barrier and invade the liver, aiding cancer cell colonization.
- Bacteria can protect cancer cells in the bloodstream, helping them survive and settle in healthy organs. Fusobacterium nucleatum stimulates tumor cells to produce substances that promote metastasis to other tissues.
- Intratumoral bacteria can alter the properties of cancer cells, making them more aggressive and capable of spreading.
Useful article, necessary information? Share it!
Someone will also find it useful and necessary:
Reference
Broadening oncological boundaries: the intratumoral microbiota
