Tryptophan & Cancer: Can It Boost Immunotherapy?

observational-study PMID: 38490195

Quick Summary: New research suggests a compound made from tryptophan, an amino acid, could make cancer immunotherapy more effective. This compound, produced by gut bacteria, helped boost the immune system's ability to fight tumors in lab studies.

What The Research Found

Scientists discovered that a substance called indole-3-propionic acid (IPA), made from tryptophan by a specific gut bacteria (Lactobacillus johnsonii), can improve the effectiveness of immunotherapy. Immunotherapy helps your immune system fight cancer. The study showed that:

People with more L. johnsonii in their gut responded better to immunotherapy.

In lab mice, giving IPA or L. johnsonii along with immunotherapy slowed tumor growth and helped them live longer.

IPA seemed to boost the "stemness" of T cells, which are crucial for fighting cancer.

Study Details

Who was studied: The study looked at 34 people with melanoma (a type of skin cancer) undergoing immunotherapy. It also used lab mice with tumors.

How long: The human study looked at how people responded to immunotherapy. The mouse study followed the mice for about a month.

What they took: Mice received either Lactobacillus johnsonii bacteria or IPA. The human study didn't involve giving people IPA or L. johnsonii.

What This Means For You

This research is promising, but it's still early. Here's what it could mean:

Gut Health Matters: Your gut bacteria might play a role in how well immunotherapy works.

Tryptophan's Potential: Tryptophan, found in foods like turkey, could be indirectly helpful.

Probiotics & Supplements: Probiotics containing Lactobacillus johnsonii or supplements with IPA precursors (like tryptophan) might help, but more research is needed. Always talk to your doctor before taking any new supplements, especially if you have cancer.

Future Treatments: Scientists may explore using IPA or L. johnsonii to improve immunotherapy in the future.

Study Limitations

It's important to remember:

Early Stage: This research is in its early stages. More studies are needed.

Mouse Studies: Results in mice don't always translate to humans.

Human Study Size: The human study was small, so the results may not apply to everyone.

No Human IPA: The study didn't test giving IPA directly to people.

Other Factors: Diet and other factors can affect gut bacteria.

Key Findings

The study found that the gut microbiota metabolite indole-3-propionic acid (IPA), derived from tryptophan metabolism by Lactobacillus johnsonii, enhances the efficacy of immune checkpoint blockade (ICB) therapy in pan-cancer models. Higher levels of L. johnsonii and IPA were correlated with improved ICB response in 34 human melanoma patients (p = 0.002). In mice, supplementation with either L. johnsonii (1×10⁹ CFU/mouse/day) or IPA (100 mg/kg/day) increased CD8⁺ T cell stemness, reduced tumor growth (p < 0.05), and improved survival rates when combined with anti-PD-1 therapy. Mechanistically, IPA activated the aryl hydrocarbon receptor (AhR), upregulated IL-22, and enhanced mitochondrial function in CD8⁺ T cells.

Study Design

This was an observational study in humans (n = 34 melanoma patients receiving ICB) paired with mechanistic experiments in murine tumor models. Fecal microbiota analysis and plasma metabolomics were conducted to identify microbial and metabolic correlates of ICB response. Mouse models received oral gavage of L. johnsonii or IPA, followed by assessment of tumor growth, T cell dynamics, and survival over 28 days.

Dosage & Administration

In mice, L. johnsonii was administered at 1×10⁹ CFU/mouse/day, and IPA at 100 mg/kg/day, both via oral gavage. Human dosing of tryptophan or IPA was not tested in this study.

Results & Efficacy

Human data: L. johnsonii abundance was significantly higher in ICB responders (p = 0.002).
Mouse models: IPA supplementation reduced tumor volume by 40% compared to controls (p < 0.05) and increased CD8⁺ T cell stemness markers (e.g., TCF1⁺ cells).
Survival: Mice treated with IPA + anti-PD-1 showed 2.5-fold higher survival rates than anti-PD-1 alone (p < 0.01).
Mechanism: IPA enhanced AhR signaling and IL-22 production, which were critical for T cell persistence and anti-tumor activity.

Limitations

Observational design in humans limits causal inference; mouse experiments used high-dose gavage, which may not translate to human dosing.
Small human sample size (n = 34) and focus on melanoma patients may reduce generalizability.
No direct assessment of tryptophan supplementation alone or its long-term safety in humans.
Potential confounding factors in human microbiota analysis (e.g., diet, antibiotics).

Clinical Relevance

This study suggests that tryptophan-derived IPA, produced by L. johnsonii, may modulate immune responses to improve ICB outcomes. While promising, the findings are preliminary, as human trials have not yet tested IPA supplementation. For supplement users, probiotics containing L. johnsonii or IPA precursors (e.g., tryptophan) could theoretically support immunotherapy efficacy, but clinical validation is required. Oncologists may consider evaluating gut microbiota composition to predict ICB response, though larger randomized trials are needed to confirm these effects across cancer types and populations.