Taurine Fuels or Fights Lung Cancer Depending on Immune Status and Dose

Lung cancer remains the leading cause of cancer-related death worldwide, and understanding how metabolites influence tumor progression is critical for developing better interventions. Taurine, a sulfonic amino acid found abundantly in tissues and widely consumed in energy drinks and supplements, was previously identified at elevated levels in the plasma of lung cancer patients — an association whose mechanistic significance was unknown until this study.

Using subcutaneous LLC-xenograft models in both immune-competent C57BL/6 mice and immune-deficient nude mice, the researchers administered taurine across a dose range (25–400 mg/kg, i.p.) as well as taurine-infused beverages. Strikingly, low doses of taurine (25 mg/kg) and equivalent doses via taurine beverages significantly accelerated tumor growth in C57 mice, while the pro-tumor effect waned at higher doses (200–400 mg/kg). This dose-dependent dual behavior was not observed in nude mice, pointing to the immune microenvironment as the decisive factor.

RNA sequencing of tumor tissues across five experimental groups revealed that in immune-competent mice, taurine modulated the Nfe2l1 (Nrf1)-ROS-PD-1 axis. Low-dose taurine upregulated PD-1 expression on both CD4+ and CD8+ T cells in peripheral blood, consistent with enhanced immune checkpoint activity and T-cell exhaustion that would facilitate tumor immune escape. High-dose taurine paradoxically reduced this effect. Flow cytometric analysis confirmed elevated PD-1 levels on T cells in the low-dose group. Plasma ROS levels also tracked with taurine dose and immune status, supporting the Nfe2l1-ROS mechanistic link. In immune-deficient nude mice, the dominant mechanism shifted: taurine suppressed tumor growth primarily through inhibition of NF-κB-mediated inflammatory signaling rather than through Nfe2l1-driven immune modulation.

Analysis of TCGA lung cancer RNA-seq data (n=1,017 samples) showed that Nfe2l1 expression is highly correlated with key taurine metabolism pathway genes. Immunohistochemistry on tissues from 129 NSCLC patients (Taihe Hospital, 2014–2017) revealed that both Nfe2l1 gene and protein expression declined toward normal levels as patients aged, and critically, Nfe2l1 lost its anti-tumor function in older patients. This age-dependent shift in Nfe2l1 activity may explain why taurine's effects on lung cancer are context-dependent across patient demographics.

These findings have important clinical implications. Taurine-containing energy drinks and supplements — consumed widely across all age groups — may inadvertently accelerate lung cancer progression in younger, immune-competent patients by enhancing PD-1-mediated immune evasion. Conversely, in older or immunocompromised patients, taurine may be less harmful or even modestly beneficial through its anti-inflammatory properties. The authors propose taurine as a candidate prognostic biomarker and urge caution among lung cancer patients regarding taurine consumption, while acknowledging that further clinical validation is necessary.