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. 2025 Apr;174(4):450-461.
doi: 10.1111/imm.13894. Epub 2025 Jan 19.

Mechanism Study of E2F8 Activation of SPC25-Mediated Glutamine Metabolism Promoting Immune Escape in Lung Adenocarcinoma

Machang Luo  1 , Lingyan Xie  1 , Baoyan Lin  2 , Xia Su  1 , Rongzhang Liang  1 , Zhiyi Ma  1 , Youtang Li  1
Affiliations

Mechanism Study of E2F8 Activation of SPC25-Mediated Glutamine Metabolism Promoting Immune Escape in Lung Adenocarcinoma

Machang Luo et al. Immunology. 2025 Apr.

Abstract

Tumour cell immune infiltration is linked to spindle pole component 25 (SPC25). The purpose of this work was to examine the function and molecular mechanism of SPC25 in immune escape in lung adenocarcinoma (LUAD). SPC25 expression in LUAD was examined using The Cancer Genome Atlas (TCGA) database, and RT-qPCR was used to confirm the results. The study involved the use of CD8+ T lymphocytes for immunoinfiltration analysis of SPC25, Gene Set Enrichment Analysis (GSEA) analysis of signalling pathways enriched by SPC25, identification of putative regulatory molecules of SPC25, and confirmation through the use of dual-luciferase and ChIP tests. To evaluate LUAD cell capacity for immune escape, a co-culture technique was employed. Measurements of glutamine uptake, glutamate and α-ketoglutarate levels, NADPH/NADP and GSH/GSSG ratios, and SLC1A5 expression were used to assess the levels of glutamine metabolism. LUAD had increased SPC25 expression. In LUAD cells, immune escape was facilitated by SPC25 knockdown, whereas overexpression had the reverse effect. SPC25 enrichment in the glutamine metabolism pathway was shown by GSEA analysis. Through increased glutamine metabolism brought on by SPC25 overexpression, immune escape was improved in LUAD and could be mitigated by GPNA therapy. E2F8 was also shown to be the transcription factor associated with SPC25, and they showed a binding interaction. By inhibiting glutamine metabolism through SPC25, knocking down E2F8 prevented immune escape in LUAD cells. On the other hand, the suppression of immune escape in LUAD cells caused by E2F8 knockdown was overcome by overexpression of SPC25. In LUAD, E2F8 stimulates SPC25 expression to facilitate glutamine metabolism and encourage immune escape. Our research validates a novel immune escape pathway driven by SPC25 in LUAD cells, providing LUAD patients with potentially effective immunotherapeutic approaches.

Keywords: E2F8; SPC25; glutamine metabolism; immune escape; lung adenocarcinoma.

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References

    1. A. A. Thai, B. J. Solomon, L. V. Sequist, J. F. Gainor, and R. S. Heist, “Lung Cancer,” Lancet 398, no. 10299 (2021): 535–554, https://doi.org/10.1016/S0140‐6736(21)00312‐3 From NLM Medline.
    1. L. Succony, D. M. Rassl, A. P. Barker, F. M. McCaughan, and R. C. Rintoul, “Adenocarcinoma Spectrum Lesions of the Lung: Detection, Pathology and Treatment Strategies,” Cancer Treatment Reviews 99 (2021): 102237, https://doi.org/10.1016/j.ctrv.2021.102237.
    1. A. Anichini, V. E. Perotti, F. Sgambelluri, and R. Mortarini, “Immune Escape Mechanisms in Non Small Cell Lung Cancer,” Cancers (Basel) 12, no. 12 (2020): 3605, https://doi.org/10.3390/cancers12123605 From NLM PubMed‐not‐MEDLINE.
    1. J. M. Pitt, A. Marabelle, A. Eggermont, J. C. Soria, G. Kroemer, and L. Zitvogel, “Targeting the Tumor Microenvironment: Removing Obstruction to Anticancer Immune Responses and Immunotherapy,” Annals of Oncology 27, no. 8 (2016): 1482–1492, https://doi.org/10.1093/annonc/mdw168 From NLM Medline.
    1. F. Klemm and J. A. Joyce, “Microenvironmental Regulation of Therapeutic Response in Cancer,” Trends in Cell Biology 25, no. 4 (2015): 198–213, https://doi.org/10.1016/j.tcb.2014.11.006 From NLM Medline.

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