Abstract
Although immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small cell lung cancer (NSCLC), the prognostic tools for programmed death-ligand 1 (PD-L1), the only approved biomarker, remain limited. We comprehensively evaluated the prognostic impact of sarcopenia and various blood biomarkers in 74 NSCLC patients receiving first-line ICIs. Sarcopenia was diagnosed using dual-energy X-ray absorptiometry. Cytokines and myokines in peripheral blood samples were assessed using Enzyme-linked immunosorbent assay (ELISA) and cytometric bead array, while lymphocyte subsets were characterized using flow cytometry. Sarcopenia group had significantly shorter progression-free survival (PFS) (P = 0.018). Sarcopenia was revealed as an independent poor prognostic factor for PFS (HR 2.63, 95% CI 1.19−5.8; P = 0.017). Patients with sarcopenia showed elevated levels of inflammatory cytokines (interleukin (IL)-6, IL-8, IL-10, IL-15, and tumor necrosis factor). Furthermore, sarcopenia index and muscle mass were negatively correlated with exhausted CD8 + T cells (CD8 + TIGIT+). The sarcopenia with high TIGIT expression group exhibited the worst prognosis (HR 3.5, P = 0.0087). Sarcopenia, immune-related blood biomarkers and high TIGIT expression were identified as independent poor prognostic factors in advanced NSCLC patients receiving first-line ICI therapy.
Data availability
The datasets used and analyzed in the current study are available from the corresponding authors upon reasonable request.
Abbreviations
- ASM:
-
Appendicular skeletal muscle mass
- BMI:
-
Body mass index
- CI:
-
Confidence interval
- DXA:
-
Dual-energy X-ray absorptiometry
- EDTA:
-
Ethylenediaminetetraacetic acid
- ELISA:
-
Enzyme-linked immunosorbent assay
- EMT:
-
Epithelial-mesenchymal transition
- HR:
-
Hazard ratio
- ICI:
-
Immune checkpoint inhibitor
- ICD:
-
International classification of diseases
- IFN:
-
Interferon
- IL:
-
Interleukin
- NSCLC:
-
Non-small cell lung cancer
- PBMC:
-
Peripheral blood mononuclear cell
- PBS:
-
Phosphate-buffered saline
- PD-L1:
-
Programmed cell death ligand 1
- PFS:
-
Progression-free survival
- PPP:
-
Platelet-poor plasma
- RCT:
-
Randomized controlled trial
- TNF:
-
Tumor necrosis factor
- Treg :
-
T-regulatory lymphocyte
- TTE :
-
Terminally differentiated effector T cell
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Acknowledgements
We thank all the volunteers who consented to participate in this study.
Funding
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Ministry of Education [Grant Numbers NRF-2022R1A6A1A03046247 and RS-2024-00451303] and the Ministry of Science and ICT [Grant Number RS-2024-00457079], Republic of Korea.
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**Jieun Park: ** Conceptualization (equal), Methodology (equal), Formal analysis (equal), Investigation (equal), Visualization (equal), Writing - Review and editing (equal). **Juwhan Choi: ** Conceptualization (equal), Methodology (equal), Formal analysis (equal), Investigation (equal), Visualization (equal), Writing - Original draft preparation (lead). **Seunghun Lee: ** Methodology (equal), Formal analysis (equal). **Jihyun Park: ** Methodology (equal), Formal analysis (equal **). Chae Rin Kim: ** Methodology (equal), Formal analysis (equal). **Yulim Lee: ** Methodology (equal), Formal analysis (equal). **Young Kee Shin: ** Conceptualization (equal), Writing - Review and editing (equal), Supervision (equal). **Sung Yong Lee: ** Conceptualization (equal), Writing - Review and editing (equal), Supervision (equal). All the authors have read and agreed to the published version of this manuscript.
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Park, J., Choi, J., Lee, S. et al. Prognostic impact of sarcopenia and blood biomarkers in advanced non-small cell lung cancer on first-line immune checkpoint inhibitors. Sci Rep (2026). https://doi.org/10.1038/s41598-026-43870-5
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DOI: https://doi.org/10.1038/s41598-026-43870-5
