A Research Review of Mycolicibacteria in Cancer Treatment

Bacteria have played a surprising role in medicine for over a century, from the development of antibiotics to their use in immunotherapy. Among them, mycobacteria have drawn attention for their ability to stimulate the immune system and enhance cancer treatments.

While Bacillus Calmette-Guérin (BCG) therapy has long been a standard treatment for bladder cancer, new research suggests that other non-tuberculous mycobacteria (NTM) may offer similar or even superior benefits in immunotherapy.

At the same time, mycolicibacteria, a specific subgroup of mycobacteria, which immy contains, are being explored for their effects on immune modulation and cancer resilience. Scientists are now investigating how these bacteria interact with the immune system, how they could complement existing treatments, and whether they might provide a breakthrough in cancer care. [1]

How Mycobacteria and Mycolicibacteria Stimulate the Immune System to Fight Cancer

The immune system is constantly scanning the body for threats, including cancerous cells, but tumors develop sophisticated ways to evade detection. Immunotherapies such as checkpoint inhibitors, a class of immunotherapy drugs designed to help the immune system recognize and attack cancer cells more effectively, attempt to counteract this immune suppression, but their effectiveness varies widely among patients. This is where bacteria-based therapies could make a difference. By engaging key immune pathways, these bacteria can help wake up the body’s natural defenses against cancer. [2]

One of the ways mycobacteria support the immune response is by stimulating antigen-presenting cells like macrophages and dendritic cells, which are responsible for recognizing abnormal cells and alerting the rest of the immune system. This activation leads to the release of critical signaling molecules, such as IL-2, TNF-α (alpha), and IFN-γ (gamma), which strengthen anti-tumor activity.[3] Research has shown that mycolicibacteria, in particular, enhance Treg (regulatory T-cell) production, reducing excessive inflammation while preserving immune function. [4]

Additionally, mycobacteria-induced inflammation increases CD4+ and CD8+ T-cell activity, which play crucial roles in identifying and destroying cancer cells.[5] By altering the tumor microenvironment, mycolicibacteria help shift immune cells out of a suppressed state, ensuring they remain active in recognizing and eliminating cancer cells.[6]

One of the greatest challenges in cancer immunotherapy is that tumors often develop resistance to checkpoint inhibitors, which are drugs designed to block proteins that suppress immune responses. Recent studies suggest that mycobacteria could help overcome this resistance by re-training the immune system, increasing response rates, and making tumors more susceptible to treatment. [7]

BCG Therapy: A Proven Model for Mycobacteria-Based Cancer Treatment

BCG therapy, derived from Mycobacterium bovis, has been successfully used to treat non-muscle invasive bladder cancer (NMIBC) for decades. By injecting BCG directly into the bladder, doctors can provoke an immune response that not only attacks cancer cells but also helps prevent recurrence.[8]

BCG works by binding to urothelial cells and triggering an immune response, leading to the recruitment of macrophages and T cells. Over time, this treatment helps establish long-term immune memory, reducing the risk of cancer returning. Given its effectiveness, researchers are now looking into ways to improve upon BCG therapy, such as combining it with other treatments or engineering new bacterial strains that could provide similar benefits with fewer side effects.[9]

Beyond BCG: The Potential of Non-Tuberculous Mycobacteria and Mycolicibacteria in Cancer Therapy

While BCG has been the most widely studied mycobacterium in cancer therapy, researchers are now exploring the potential of other species, particularly Mycobacterium brumae. This non-tuberculous mycobacterium (NTM) has been shown to inhibit bladder cancer cell migration and invasion, making it a promising alternative to BCG, especially for patients who cannot tolerate traditional BCG therapy.[10]

In addition to NTMs, mycolicibacteria are gaining attention for their ability to modulate the immune system and improve resilience against chronic diseases, including cancer. Studies indicate that mycolicibacteria help regulate inflammation, enhance immune surveillance, and support serotonin production, which can influence stress resilience and overall health.[11]

Preliminary studies suggest that mycobacteria may have a broader role in cancer treatment beyond bladder cancer. For example, they have been found to reduce tumor growth in other cancers, including lung and melanoma. Scientists are also investigating whether they could be used to enhance checkpoint inhibitors, as recent studies show that modifying the gut microbiome—where mycolicibacteria naturally interact with immune cells—may improve responses to immunotherapy.[12]

Another intriguing possibility is the use of mycobacteria as a drug delivery system, engineering bacteria to carry cancer-fighting molecules directly into tumors. Because mycobacteria naturally stimulate the immune system, they could serve as both an immunotherapy and a targeted drug carrier, making treatments more precise and effective.[13]

1. Bach-Griera, M., Hernández, A., Julián, E. (2024). Mycobacteria Treatment Inhibits Bladder Cancer Cell Migration. International Journal of Molecular Sciences.

2. Lee, A., et al. (2023). Brain–Gut–Microbiota Axis. Korean Journal of Gastroenterology.

3. Kunjarwal, R., et al. (2017). Microbial Therapeutics in Oncology. Springer Nature.

4. Fol, M., et al. (2024). Dual Nature of Relationship between Mycobacteria and Cancer. International Journal of Molecular Sciences.

5. Song, Minyang., et al. (2023). Influence of the Gut Microbiome, Diet, and Environment on Risk of Colorectal Cancer. Gastroenterology.

6. Zhang, X., et al. (2024). Pancreatic Cancer in Young Adults: An Evolving Entity. American Journal of Cancer Research.

7. Zaborowski, A., et al. (2024). Characteristics of Early-Onset vs Late-Onset Colorectal Cancer: A Review. Jama Surgery.

8. Vishwanath, A., et al. (2023). Early-Onset Gastrointestinal Malignancies. Cancers.

9. Ting, NL., et al. (2024). Cancer Pharmacomicrobiomics: Targeting Microbiota to Optimise Cancer Therapy Outcomes. Cancer Immunology Research.

10. Saraiva, MR., et al. (2024). Early-Onset Colorectal Cancer: A Review of Current Knowledge. World Journal of Gastroentrology.

11. Loh, J.S., et al. (2024). Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Nature.

12. Mellman, I., et al. (2024). The Cancer-Immunity Cycle: Indication, Genotype, and Immunotype. Immunity.

13.  Hammer, C., et al. (2024). Human Genomics and the Cancer–Immune Set Point. Cancer Immunology Research.