bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2026–01–18
two papers selected by
the Muñoz-Pinedo/Nadal (PReTT) lab, L’Institut d’Investigació Biomèdica de Bellvitge
  1. Metabolic reprogramming signature predicts immunotherapy efficacy in lung adenocarcinoma: Targeting SLC25A1 to overcome immune resistance.
  2. A comprehensive analysis of the correlation between plasma cytokines/chemokines and tumor immune microenvironment signature influences the response of checkpoint inhibitors in advanced non-small-cell lung cancer.
  1. Chin J Cancer Res. 2025 Dec 30. 37(6): 1000-1019
    Metabolic reprogramming signature predicts immunotherapy efficacy in lung adenocarcinoma: Targeting SLC25A1 to overcome immune resistance.
    Pengpeng Zhang, Xiaoqing Liang, Bicheng Ye, Xiaofei Wang, Yijie Wang, Zetian Gong, Yuming Huang, Jinyang Liu, Chenjun Huang, Peng Luo.
       Objective: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Despite significant advances in immunotherapy, treatment responses vary substantially among individuals. Metabolic reprogramming, as a hallmark of cancer, plays a crucial role in tumor progression and immune evasion. However, the interplay between metabolic features and tumor immune microenvironment in LUAD remains to be systematically elucidated.
    Methods: We analyzed data from 1,231 LUAD patients across seven global cohorts and developed an integrated Metabolism-Related Signature (iMRS) using machine learning approaches based on 114 metabolic features. The signature's ability to predict immunotherapy response was validated using 9 immunotherapy cohorts (n=712, including LUAD, melanoma, and glioma). An in-house LUAD tissue cohort (n=146) confirmed the prognostic significance of SLC25A1, a key gene within the signature, and its spatial relationship with immune cells. In vivo and in vitro experiments investigated SLC25A1's role in cancer promotion, immune exclusion, and its impact on programmed cell death protein 1 (PD-1) therapy efficacy.
    Results: iMRS demonstrated superior prognostic performance in LUAD patients, outperforming 129 published LUAD signatures. In immunotherapy cohorts, responders showed significantly lower iMRS scores. High iMRS was associated with reduced immune activity and "cold" tumor characteristics. SLC25A1 (correlation coefficient=0.54, P<0.05), a key gene in the signature, showed the highest expression in CD8 desert phenotype and correlated with poor prognosis. Multiplexed immunofluorescence revealed exclusion patterns between SLC25A1 and immune cells (CD4+ T cells and CD20+ B cells). SLC25A1 knockdown reduced lung metastasis and enhanced anti-PD-1 efficacy by increasing CD8+ T cell abundance and cytotoxicity [increased interferon-γ (IFN-γ)+/GZMB+ CD8+ T cells].
    Conclusions: iMRS provides personalized immunotherapy prediction for LUAD patients. SLC25A1, identified as a novel immune-exclusion related oncogene, represents a promising therapeutic target for LUAD treatment.
    Keywords:  Lung adenocarcinoma; SLC25A1; immunotherapy response; metabolism signature; tumor immune microenvironment
    DOI:  https://doi.org/10.21147/j.issn.1000-9604.2025.06.11
  2. Clin Transl Immunology. 2026 ;15(1): e70076
    A comprehensive analysis of the correlation between plasma cytokines/chemokines and tumor immune microenvironment signature influences the response of checkpoint inhibitors in advanced non-small-cell lung cancer.
    Van Hieu Mai, Marisa Prasanpanich, Nicha Zungsontiporn, Krittiya Korphaisarn, Piyada Sitthideatphaiboon, Chatchawit Aporntewan, Poonchavist Chantranuwat, Nattiya Hirankarn, Chanida Vinayanuwattikun.
       Objectives: Circulating cytokines/chemokines are linked to checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). The tumor-immune microenvironment (TIME) plays a significant role in modulating a broad range of cytokines and chemokines. This study aimed to explore the crosstalk between circulating cytokines/chemokines and TIME, related to ICIs outcomes.
    Methods: We conducted a prospective cohort study of 81 participants with advanced or recurrent NSCLC who received ICIs. Pretreatment comprehensive 27 cytokines/chemokines analysis, immunohistochemistry (IHC) for CD8, Treg/FOXP3, and PD-L1(22C3) TPS, and RNA sequencing were conducted. Demographic characteristics were integrated in the analysis to define the crosstalk of significant TIME-related signatures. Circulating neutrophil-to-lymphocyte ratio (NLR) and IHC tumor-infiltrated neutrophil density were evaluated to correlate systemic and local inflammatory states with ICIs response.
    Results: Pretreatment plasma IL-6 and IL-8 were the significant cytokines correlated with surrogate ICIs responses and ICIs progression-free survival (PFS). Despite several correlations between cytokines/chemokines and CD8+ TILs, Treg/FOXP3+ TILs, neither pretreatment IL-6 nor IL-8 was correlated with intra-tumoral or stromal Treg/FOXP3+ TILs, CD8+ TILs, and PD-L1. Four active neutrophil-related gene signatures overlapped and were significantly correlated with better ICIs outcomes and lower IL-6 levels. Among 69 genes in 4 neutrophil-related gene signatures, the overexpression of TREM1, SORL1, and HSD17B11 significantly contributed and inversely correlated with CIBERSORT memory B cells. Clinically, the stratification by low levels of IL-6/IL-8 and low NLR identified a subgroup with significantly improved survival outcomes, whereas IHC tumor-infiltrated neutrophil counts did not show a similar association.
    Conclusion: Our study reveals a potential mechanistic axis linking circulating IL-6 and IL-8 to tumor-associated neutrophils, memory B cells, and therapeutic response. These findings underscore the crucial role of synergistic treatment in augmenting the efficacy of ICIs. The crosstalk between neutrophils and B cells in the orchestration of ICIs therapy for NSCLC was further elucidated through the roles of HSD17B11, SORL1, and TREM1.
    Keywords:  cytokines; immunotherapy; non‐small‐cell lung cancer; tumor‐immune microenvironment
    DOI:  https://doi.org/10.1002/cti2.70076
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