Enterococcus hirae and Barnesiella intestinihominis in CTX Immunomodulation

The Role of CTX and Gut Microbiota in Cancer Treatment

Cancer is a complex and multifaceted disease that requires diverse treatment strategies. Immunotherapy, which harnesses the body's immune system to fight cancer, has emerged as a promising approach. By stimulating or restoring the immune system's ability to detect and destroy cancer cells, immunotherapy can complement traditional treatments like chemotherapy and radiation.

In recent years, the gut microbiota, the diverse community of microorganisms residing in the gastrointestinal tract, has gained attention for its significant role in human health and disease. These microbial populations are recognized as key players in shaping the immune system and influencing metabolic processes. Research has revealed that the composition and activity of the gut microbiota can impact the effectiveness of cancer treatment, highlighting the intricate interplay between our microbial inhabitants and cancer therapy.

Cyclophosphamide (CTX) is a well-established chemotherapeutic agent used in various cancer treatments. Its mechanism of action involves the alkylation of DNA, leading to the disruption of DNA replication and cell death. Beyond its direct cytotoxic effects, CTX is known for its immunomodulatory properties, such as selectively depleting regulatory T cells (Tregs) and enhancing the activity of cytotoxic T cells, thereby boosting the immune response against cancer cells. Recent studies have highlighted the role of the gut microbiota in modulating the efficacy of CTX. The gut microbiota plays a crucial role in maintaining immune homeostasis, and the anticancer effects of CTX are partly dependent on the presence of specific gut bacterial species. Understanding the relationship between the gut microbiota and cancer treatment is crucial for developing more effective and personalized treatment strategies for cancer patients.

Enterococcus hirae (E. hirae) and Barnesiella intestinihominis (B. intestinihominis) in Immunomodulation

E. hirae and B. intestinihominis are two gut bacteria that have recently been identified as significant contributors to the immunomodulatory effects of CTX These bacteria, residing in different parts of the gut, interact with the host's immune system in unique ways to enhance the efficacy of CTX.

E. hirae, primarily found in the small intestine, has been shown to translocate to secondary lymphoid organs following CTX treatment. This translocation triggers specific immune responses that are beneficial for anti-cancer therapy. On the other hand, B. intestinihominis, which resides in the colon, has been associated with the promotion of IFN-gamma-producing gamma delta T cells in cancer lesions, contributing to the overall anti-tumor immune response. The mechanisms by which E. hirae and B. intestinihominis enhance the efficacy of CTX are complex and involve multiple aspects of the immune system.

E. hirae

• Translocation and Immune Activation: Following CTX treatment, E. hirae translocates from the small intestine to secondary lymphoid organs. This translocation is associated with the activation of tumor antigen-specific cytotoxic T cells (CTLs) and the generation of pathogenic Th17 (pTh17) cells.
• Modulation of T Cell Ratios: E. hirae increases the ratio of CTLs to regulatory T cells (Tregs) within the tumor microenvironment. This shift is favorable for anti-cancer immunity, as Tregs are known to suppress the immune response against tumors.
• Epithelial Layer Proliferation: E. hirae colonization leads to the proliferation of γδ T cells and CD8+ T cells in the epithelial layer, further contributing to an enhanced anti-tumor response.

B. intestinihominis

• Enhancement of Th1 and Tc1 Responses: B. intestinihominis boosts systemic polyfunctional Tc1 and Th1 cell responses, which are critical for effective anti-cancer immunity.
• Promotion of IFN-gamma-producing γδ T Cells: This bacterium promotes the infiltration of IFN-gamma-producing γδ T cells into cancer lesions, adding another layer of immune defense against tumors.
• Reduction of Tregs: Similar to E. hirae, B. intestinihominis contributes to reducing the presence of Tregs in the tumor microenvironment, thereby alleviating their suppressive effects on the immune response.

Fig. 1 E. hirae and B. intestinihominis facilitate CTX -induced therapeutic immunomodulatory effects.¹

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Clinical Implications of Gut Microbiota in Cancer Treatment

Recent clinical findings have demonstrated the predictive value of preexisting memory Th1 immune responses to E. hirae and B. intestinihominis for progression-free survival (PFS) in cancer patients undergoing chemotherapy. In a study involving 38 advanced lung and ovarian cancer patients, those with higher levels of memory Th1 cells recognizing E. hirae and B. intestinihominis post-platinum-based chemotherapy exhibited longer PFS. This correlation was not observed with Th1 cell responses to other bacteria, highlighting the specific role of E. hirae and B. intestinihominis in modulating the immune system's response to cancer.

The potential of monitoring and modulating gut microbiota as part of cancer treatment strategies is becoming increasingly evident. The gut microbiome's composition and activity can influence the effectiveness of chemotherapy and immunotherapy. By understanding the interactions between specific bacterial species and the immune system, clinicians could potentially manipulate the gut microbiota to enhance the efficacy of cancer treatments. This could involve the use of probiotics, prebiotics, or fecal microbiota transplantation to maintain or restore a beneficial microbial balance. Creative Biolabs offers a tailored selection of E. hirae products to meet your research needs, ensuring high-quality results and customer satisfaction.

Future Perspectives

Ongoing research in the field of gut microbiota and cancer immunotherapy is exploring the mechanisms by which specific bacterial species influence the immune response to cancer. The development of probiotics or microbiota-based therapies to enhance the effectiveness of cancer treatments is a promising area of investigation. These therapies could be tailored to individual patients based on their gut microbiota composition, providing a personalized approach to cancer treatment.

The concept of "oncomicrobiotics," or immunogenic commensals influencing the host-cancer equilibrium, is emerging as a potential strategy to optimize cancer therapies. Future studies will likely focus on identifying additional bacterial species that can modulate the immune system's response to cancer and determining the most effective ways to manipulate the gut microbiota to improve treatment outcomes.

Resources

Reference

1. Daillère, R., Vétizou, M., et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016, 45(4), 931-943.

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