1. Can you please briefly summarize the paper?

Our study explored the functional role of cancer-associated fibroblasts (CAFs) derived from brain metastases of non-small cell lung cancer (NSCLC) in promoting tumor progression and therapeutic resistance. We found that brain metastasis-associated CAFs (BM-CAFs) markedly enhanced NSCLC cell proliferation, migration, invasion, and resistance to both chemotherapy and radiotherapy. Mechanistically, BM-CAFs secreted two cytokines—IL-26 and CX3CL1—that activated the JAK–STAT3 and AKT–mTOR signaling pathways in tumor cells. Neutralization of these cytokines effectively suppressed these signaling cascades, reversed epithelial–mesenchymal transition (EMT) and cancer stem cell (CSC) phenotypes, and consequently reduced tumor aggressiveness. Collectively, our findings identify IL-26/CX3CL1-mediated signaling as a key driver of BM-CAF-induced tumor progression and resistance, highlighting it as a potential therapeutic target for NSCLC brain metastasis.

2. Can you please tell us the main difficulties you had in the laboratory work and how you overcame them?

The primary challenge in this study was the isolation and maintenance of patient-derived cancer-associated fibroblasts (CAFs) from brain metastasis tissues, which are typically limited in quantity and exhibit high heterogeneity. To address this, we developed a refined isolation and culture protocol that ensured fibroblast purity by confirming the expression of canonical CAF markers such as α-SMA, Vimentin, and PDGFR-β, while excluding epithelial and endothelial cell contamination. Additionally, to minimize phenotypic drift, all experiments were performed using heterogeneous CAF populations within five passages.

Another major challenge was the reconstruction of the complex brain tumor microenvironment in vitro. To overcome this limitation, we integrated RNA sequencing, in vitro co-culture systems, and in vivo xenograft models, enabling comprehensive validation of our findings across molecular, cellular, and organismal levels. This multi-model approach strengthened the reproducibility and translational relevance of our results.

3. Please introduce your laboratory, university or organization to bio-researchers in Korea.

Our research was conducted at the Department of Pathology and Neurosurgery, Chonnam National University Hwasun Hospital, in collaboration with the Medical Research Center for Immunotherapy of Cancer at Chonnam National University Medical School.
Our laboratory focuses on brain metastasis and tumor microenvironment research, especially exploring the crosstalk between cancer-associated fibroblasts (CAFs), immune cells, and tumor cells. We integrate molecular biology, bioinformatics, and translational cancer research to identify potential therapeutic targets for metastatic brain tumors.

4. Please tell us your experiences and your thoughts related to research activities abroad.

Working in an international research environment has given me exposure to diverse scientific perspectives, advanced experimental systems, and collaborative teamwork.
It improved my ability to communicate scientific ideas clearly in English and strengthened my understanding of global research standards, including data reproducibility and ethical compliance.
I believe international collaboration is essential to address complex diseases like cancer, where multidisciplinary insights make a real difference.

5. Can you provide some advice for younger scientists who have plans to study abroad?

My advice for young scientists planning to study abroad is to focus on developing both technical competence and communication skills. Mastering experimental techniques is essential, but it is equally important to express your research ideas clearly and confidently in English, as effective communication greatly enhances collaboration and scientific impact.
Remain curious, adaptable, and resilient—you will encounter cultural and academic challenges, but these experiences will help you mature as an independent researcher. Finally, seek mentors who can guide you not only in science but also in personal and professional growth, as good mentorship can make a lasting difference in your research journey.

6. Future plan?

I plan to continue exploring how non-immune stromal cells like CAFs regulate immune suppression within the tumor microenvironment of brain metastasis.
Specifically, I aim to investigate how CAF-secreted factors affects immune cell polarization and contributes to therapy resistance.
Ultimately, my goal is to develop targeted strategies that can reprogram the tumor microenvironment to improve the efficacy of immunotherapy in metastatic brain cancer.

7. Do you have anything else that you would like to tell Korean scientists and students?

Korean research infrastructure and scientific talent are exceptional. I would encourage scientists in Korea to embrace multidisciplinary approaches and international collaboration.
Also, never underestimate the importance of perseverance—even small, incremental progress in the lab can lead to impactful discoveries.
Science is not just about experiments, but about curiosity, teamwork, and continuous learning.