Microbe inhabitants in the gut may stimulate the immune system's response to launch an attack on cancerous cells.
Unleashing the Power within: Gut Bacteria and Cancer Immunotherapy
Worldwide research sheds light on gut bacteria that can supercharge the immune system's battle against cancer, paving the way for more efficient and personalized cancer treatments.
Immunotherapy, treating diseases by boosting the body's inherent defense mechanisms, is the focus here. One popular immunotherapy approach employs drugs known as immune checkpoint inhibitors. These drugs target proteins produced by cancer cells that shield them from immune cells' attacks.
However, not every cancer patient responds well to immune checkpoint inhibitor therapy, and these treatments can have severe side effects. To tackle this issue, a groundbreaking study published in Nature Communications offers insights that might help predict which patients would respond best to this treatment.
Researchers investigated the molecular processes governing the interaction between gut bacteria and the immune system. The study was led by a team from Sanford Burnham Prebys Medical Discovery Institute in La Jolla, CA, in conjunction with three hospitals.
The Power Struggle: Gut Bacteria, Immune System, and Melanoma
Thomas Gajewski, a professor of cancer immunotherapy at the University of Chicago, IL, describes the study as an essential step towards expanding the number of people who can benefit from immunotherapy.
The investigators identified 11 gut bacteria strains that, when interacting with the immune system, helped suppress melanoma tumor growth in mice. They also highlighted the unfolded protein response (UPR) as a crucial link between gut bacteria and the immune system's ability to combat cancer.
UPR is a cellular process that ensures protein populations remain stable and healthy by eliminating incorrectly folded proteins caused by cell stress.
Senior study author Ze'ev Ronai, a professor at Sanford Burnham Prebys, suggests that UPR activity could serve as a marker for selecting melanoma patients who are more likely to benefit from immune checkpoint therapy. Lower UPR activity was observed in individuals with melanoma whose cancer responded well to the treatment, indicating a potential correlation.
A Need for Improvement: Expanding the Reach of Checkpoint Inhibitor Therapy
Melanoma, while less common than most types of skin cancer, tends to be aggressive and deadly. Accounting for only a fraction of all skin cancers, melanoma remains the leading cause of skin cancer-related deaths in the United States.
Immediate treatment with immune checkpoint inhibitors has significantly improved survival rates for melanoma patients. However, melanoma's ability to spread rapidly and the therapy's limited efficacy and side effects continue to pose challenges. The therapy works effectively for roughly half of all cases, with potential autoimmune reactions, limited response duration, and therapy resistance remaining concerns.
Previous research has shown that specific strains of gut bacteria can either boost or weaken the effects of immunotherapy. Antibiotics and certain probiotics can also reduce its effectiveness.
A Useful Tool: The Study Mouse Model
In their investigation, the team utilized mice lacking the RING finger protein 5 (RNF5), which aids cells in removing incorrectly folded proteins. Mice with intact immune systems and gut microbiomes were found to inhibit melanoma tumor growth. However, upon exposure to mice lacking RNF5 or antibiotics, the mice lost their ability to combat melanoma tumors, indicating the crucial role of gut microbes in antitumor defenses.
Further exploration revealed the involvement of several components of the immune system in both the gut and the reduction in UPR activity, which in turn activated immune cells. By transplanting the 11 identified bacterial strains to germ-free mice, the team triggered an antitumor response and reduced melanoma tumor growth. Lastly, the researchers confirmed the results using tissue samples from three separate groups of melanoma patients who underwent immunotherapy.
The investigations suggest that UPR components could potentially serve as biomarkers to predict which patients may benefit most from immunotherapy. Future research aims to identify the antitumor molecules produced by gut bacteria and determine how probiotics might increase their effectiveness in melanoma patients.
"Our study establishes a formal link between the microbiome and antitumor immunity and points to the role of the UPR in this process, answering a long-sought question for the field," says Prof. Ze'ev Ronai.
- The study published in Nature Communications explores the interaction between gut bacteria and the immune system in the fight against cancer.
- One popular approach in immunotherapy employs immune checkpoint inhibitors, targeting proteins produced by cancer cells.
- Some cancer patients may not respond well to immune checkpoint inhibitor therapy, and side effects can be severe.
- The study was led by a team from Sanford Burnham Prebys Medical Discovery Institute, with collaboration from three hospitals.
- Thomas Gajewski, a professor of cancer immunotherapy, suggests the study could benefit more people with cancer through immunotherapy.
- Eleven gut bacteria strains were identified that help suppress melanoma tumor growth in mice.
- The unfolded protein response (UPR) is a crucial link between gut bacteria and the immune system's ability to combat cancer.
- UPR activity could serve as a marker for melanoma patients who may respond best to immune checkpoint therapy.
- Lower UPR activity was observed in individuals with melanoma whose cancer responded well to the treatment.
- Melanoma tends to be aggressive and deadly.
- Immediate treatment with immune checkpoint inhibitors has improved survival rates for melanoma patients, but challenges remain.
- Specific strains of gut bacteria can boost or weaken the effects of immunotherapy.
- Antibiotics and certain probiotics can reduce the effectiveness of immunotherapy.
- The team used mice lacking RNF5, a protein that aids in removing incorrectly folded proteins, in their investigation.
- Mice with intact immune systems and gut microbiomes inhibited melanoma tumor growth.
- Exposure to mice lacking RNF5 or antibiotics caused the mice to lose the ability to combat melanoma tumors.
- Several components of the immune system are involved in both the gut and the reduction in UPR activity.
- Transplanting the 11 identified bacterial strains to germ-free mice triggered an antitumor response and reduced melanoma tumor growth.
- The researchers confirmed the results using tissue samples from three separate groups of melanoma patients.
- UPR components could potentially serve as biomarkers to predict which patients may benefit most from immunotherapy.
- The study underscores the importance of gut bacteria in antitumor defenses.
- Future research aims to identify the antitumor molecules produced by gut bacteria and determine how probiotics might increase their effectiveness in melanoma patients.
- Ze'ev Ronai, the senior study author, describes the study as an essential step towards expanding the reach of checkpoint inhibitor therapy.
- Melanoma accounts for only a fraction of all skin cancers but is the leading cause of skin cancer-related deaths in the United States.
- The World Health Organization categorizes melanoma as a metastatic cancer, making it difficult to treat effectively.
- Understanding the role of gut bacteria in cancer immunotherapy could lead to more personalized and successful treatments for patients with melanoma.
