한빛사논문
- 조회155
Se-Hoon Lee a,b,1, Sujeong Kim c,1, Jueun Lee d,1, Yunjae Kim c,1, Yanghyun Joo c, Jun-yeong Heo b, Heeyeon Lee d, Charles Lee e, Geum-Sook Hwang d,f, Hansoo Park c,g
aDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
bDepartment of Health Sciences and Technology, Samsung Advanced Institute of Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea
cDepartment of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, South Korea
dIntegrated Metabolomics Research Group, Western Seoul Center, Korea Basic Science Institute, Seoul, South Korea
eThe Jackson Laboratory for Genomic Medicine, 10 Discovery Drive, Farmington, CT 06032, USA
fCollege of Pharmacy, Chung-Ang University, Seoul 06974, South Korea
gGenome&Company, GWANGGYO FLAX DESIAN 7F, Changnyong-daero 256beon-gil 50, Yeongtong-gu, Suwon-si, Gyeonggi-do 16229, South Korea
1Co-first authors
Corresponding authors: Geum-Sook Hwang, Hansoo Park
Abstract
Although immune checkpoint inhibitors (ICIs) have revolutionized immuno-oncology with effective clinical responses, only 30 to 40 % of patients respond to ICIs, highlighting the need for reliable biomarkers to predict and enhance therapeutic outcomes. This study investigated how amino acid, glycolysis, and bile acid metabolism affect ICI efficacy in non-small cell lung cancer (NSCLC) patients. Through targeted metabolomic profiling and machine learning analysis, we identified amino acid metabolism as a key factor, with histidine (His) linked to favorable outcomes and homocysteine (HCys), phenylalanine (Phe), and sarcosine (Sar) linked to poor outcomes. Importantly, the His/HCys+Phe+Sar ratio emerges as a robust biomarker. Furthermore, we emphasize the role of glycolysis-related metabolites, particularly lactate. Elevated lactate levels post-immunotherapy treatment correlate with poorer outcomes, underscoring lactate as a potential indicator of treatment efficacy. Moreover, specific bile acids, glycochenodeoxycholic acid (GCDCA) and taurolithocholic acid (TLCA), are associated with better survival and therapeutic response. Particularly, TLCA enhances T cell activation and anti-tumor immunity, suggesting its utility as a predictive biomarker and therapeutic agent. We also suggest a connection between gut microbiota and TLCA levels, with the Eubacterium genus modulating this relationship. Therefore, modulating specific metabolic pathways—particularly amino acid, glycolysis, and bile acid metabolism—could predict and enhance the efficacy of ICI therapy in NSCLC patients, with potential implications for personalized treatment strategies in immuno-oncology.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2024-10-16)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
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