In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment paradigms, especially for patients diagnosed with advanced non-small cell lung cancer (NSCLC). These groundbreaking therapies work by unleashing the immune system’s capacity to identify and fight tumor cells, offering hope where traditional treatments often fall short. However, despite their promise, ICIs are frequently accompanied by immune-related adverse events (irAEs) that challenge patient outcomes and quality of life. Against this backdrop, a novel study has emerged investigating the potential of Bojungikki-Tang (BJIKT), an ancient traditional herbal formulation, to modulate immune response and clinical outcomes when used alongside ICIs in NSCLC patients.

This exploratory, randomized pilot study, conducted across multiple centers, sought to assess the safety and immunomodulatory effects of BJIKT—a well-known herbal remedy used traditionally in East Asian medicine for its anti-inflammatory and fatigue-relieving properties. The study specifically targeted patients with advanced NSCLC receiving atezolizumab monotherapy, an anti-PD-L1 checkpoint inhibitor widely used in clinical oncology. By integrating this herbal medicine with modern immunotherapy, the researchers aimed to explore if BJIKT could mitigate some common treatment-related adverse events such as fatigue and muscle wasting, while potentially enhancing immune activation.

The trial enrolled 28 patients who were randomly assigned to receive either BJIKT or a placebo, with both groups continuing standard atezolizumab therapy. Throughout the study, the team meticulously monitored adverse events (AEs), immune-related adverse events (irAEs), fatigue levels, and the progression of muscle loss, aiming to uncover interactions between the herbal treatment and immune checkpoint blockade. Beyond clinical symptomatology, a subset of patients underwent detailed immune profiling to shed light on the cellular immune mechanisms potentially influenced by BJIKT.

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Findings revealed that adverse events were prevalent in over half of participants, a not unexpected outcome given the aggressive nature of cancer immunotherapy. Intriguingly, the BJIKT group exhibited a higher incidence of AEs (64.29%) compared to the placebo group (42.86%), though the majority of these events were mild to moderate and resolved by the conclusion of the trial. This raises important safety considerations but also underscores the complex interplay between herbal compounds and immune modulation therapies, warranting further pharmacovigilance in larger cohorts.

From an efficacy standpoint, the objective response rate (ORR) and disease control rate (DCR) were numerically higher in the BJIKT-treated group—16.67% versus 8.33% for ORR and 41.67% versus 25% for DCR compared to placebo—though these differences did not reach statistical significance. These encouraging trends suggest that BJIKT might augment tumor growth control during ICI therapy, possibly by enhancing the host immune system’s anti-tumor prowess. Nonetheless, the lack of statistical significance tempers overenthusiasm and highlights the exploratory nature of this pilot trial.

One of the more compelling aspects of the study lies in its immunological analyses. The researchers detected a significant reduction in PD-1 positive CD8+ T cells in patients receiving BJIKT, implying a decrease in T cell exhaustion—a state where T cells become less functional due to chronic antigen exposure, commonly seen in cancer. This finding indicates that BJIKT may reinvigorate cytotoxic T cells, a pivotal cell population responsible for directly attacking tumor cells. Conversely, while PD-1+ CD4+ T cell numbers also declined with BJIKT, this change was not statistically significant, suggesting a selective modulation of T cell subsets.

Beyond T cells, a notable increase in natural killer (NK) cell counts was observed in the BJIKT group. NK cells constitute an essential arm of innate immunity, capable of recognizing and destroying cancer cells without prior sensitization. The elevation of these effector cells may reflect enhanced innate immune surveillance facilitated by BJIKT, potentially contributing to improved tumor control in NSCLC. Moreover, immune profiling revealed trends toward increased activation of CD4+ T cells and the overall proportion of CD3+CD4+ cells, indicating a broader stimulation of helper T cell-mediated immune orchestration during treatment.

BJIKT’s capacity to alleviate fatigue and muscle loss—common debilitating symptoms experienced by patients undergoing immunotherapy—was also examined. While the herbal treatment showed a trend toward mitigating these symptoms, the changes were not statistically significant. Still, these observations correlate with BJIKT’s traditional use in managing fatigue and chronic inflammation, suggesting it may hold supportive care value for NSCLC patients in future integrative oncology frameworks.

The study’s design as a randomized, placebo-controlled pilot trial provides valuable preliminary insights but naturally comes with limitations inherent to small sample sizes, which restrict the statistical power to detect definitive effects. However, the findings lay a foundation for subsequent larger-scale investigations to validate BJIKT’s immunomodulatory benefits and safety profile in combination with ICIs. Such follow-up trials could also dissect the molecular pathways involved, potentially revealing novel complementary mechanisms by which traditional herbal medicine synergizes with cutting-edge immunotherapies.

Notably, the interplay between BJIKT and the complex tumor-immune microenvironment highlights the exciting potential of combining phytochemicals with immuno-oncological agents. This fusion of ancient herbal wisdom with modern molecular oncology could pave the way for innovative, multi-modal cancer treatment regimens aimed at boosting efficacy while minimizing toxicities. Furthermore, the selective immune effects observed with BJIKT—specifically the reduction of immune exhaustion markers and augmentation of NK cells—underscore the importance of immune homeostasis in achieving sustained anti-tumor responses.

From a clinical perspective, this research advocates for integrating complementary therapies like BJIKT into the multidisciplinary care of NSCLC patients receiving ICIs. Positive modulation of immune function and alleviation of adverse symptom burden could improve patient adherence to therapy and quality of life. However, the necessity for rigorous validation studies, standardized herbal preparations, and mechanistic elucidations cannot be overstated before broad application.

Additionally, the trial was registered with the Clinical Research Information Service of Korea, ensuring adherence to ethical and methodological standards. Such transparency not only bolsters credibility but also facilitates collaboration, data sharing, and global efforts to refine cancer therapies. Future studies may build upon this pilot trial to design adaptive, biomarker-driven approaches targeting immune exhaustion and enhancing effector cell function in NSCLC and beyond.

In summary, this pioneering research sheds light on the prospective role of Bojungikki-Tang as an adjunctive agent capable of finely tuning the immune landscape in NSCLC patients undergoing atezolizumab therapy. While conclusive evidence remains forthcoming, the reported reductions in immune exhaustion markers and elevations in innate immune effectors inspire optimism for harnessing herbal pharmacology in the fight against lung cancer. This convergence of traditional medicine and immuno-oncology represents a fertile frontier warranting enthusiastic scientific pursuit.

As the oncology community continues to grapple with the challenges of maximizing immunotherapy benefit, findings like these energize the search for integrative strategies. Bojungikki-Tang’s ancient formula, reinterpreted through the lens of modern immune profiling, exemplifies how history may inform future breakthroughs. Clinical trials with larger cohorts, longer follow-up, and multi-omics analyses will be imperative to validate these preliminary signals and ultimately translate them into robust, patient-centered cancer care innovations.

Subject of Research: Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors

Article Title: Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors: a randomized pilot study

Article References:
Ko, M.M., Na, S.W., Yi, J.M. et al. Effects of Bojungikki-Tang on immune response and clinical outcomes in NSCLC patients receiving immune checkpoint inhibitors: a randomized pilot study. BMC Cancer 25, 1229 (2025). https://doi.org/10.1186/s12885-025-14629-4

Image Credits: Scienmag.com

DOI: https://doi.org/10.1186/s12885-025-14629-4

Tags: adverse events in cancer therapyanti-PD-L1 therapyBojungikki-Tangclinical outcomes in NSCLCfatigue management in cancerimmune checkpoint inhibitorsimmunomodulatory effectsintegrative oncologylung cancer treatmentnon-small cell lung cancerpatient quality of lifetraditional herbal medicine