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Article

Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target

1
Department of Biostatistics, School of Public Health, Harbin Medical University, Harbin 150086, China
2
Laboratory for the Study of Metastatic Microenvironments, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
3
School of Health Management, Harbin Medical University, Harbin 150086, China
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(20), 9920; https://doi.org/10.3390/ijms26209920 (registering DOI)
Submission received: 4 September 2025 / Revised: 7 October 2025 / Accepted: 10 October 2025 / Published: 12 October 2025

Abstract

Glioblastoma multiforme (GBM) is a common malignancy with poor prognosis, and exhausted T (TEX) cells, a subset of T cells characterized by progressive loss of effector functions, play a critical role in its progression. This study aimed to investigate the impact of TEX-related genes on immune function, prognosis, and drug sensitivity in GBM through multiomics analysis. Initially, we identified a novel set of TEX-related genes specific to GBM and screened hub genes (CCL5, IL18, CXCR6, FCER1G, TNFSF13B) using conventional statistical methods combined with machine learning. A prognostic risk model was subsequently constructed based on TCGA data and validated in the CGGA cohort. Single-cell and pharmacogenomic analyses revealed significant differences in tumor microenvironment composition and drug sensitivity between risk groups. Notably, Palbociclib emerged as a potential therapeutic agent targeting the novel discovered biomarker CCL5. RT-qPCR results showed that T cells with low CCL5 expression exhibited reduced expression of immune checkpoint-related genes (PD1, TIM3, LAG3) and increased expression of CD28, suggesting enhanced immune function. In conclusion, our findings highlight five hub genes as prognostic markers that could stratify GBM patients with different immune landscapes and levels of drug sensitivity. Furthermore, experimental results suggest that low CCL5 expression could alleviate T cell exhaustion and represent a promising therapeutic target, offering new strategies for improving GBM prognosis.
Keywords: GBM; exhausted T cell; multiomics; drug sensitivity; CCL5 GBM; exhausted T cell; multiomics; drug sensitivity; CCL5

Share and Cite

MDPI and ACS Style

Qin, R.; Hua, M.; Wang, Y.; Zhang, Q.; Cao, Y.; Dai, Y.; Ma, C.; Zheng, X.; Ge, K.; Zhang, H.; et al. Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target. Int. J. Mol. Sci. 2025, 26, 9920. https://doi.org/10.3390/ijms26209920

AMA Style

Qin R, Hua M, Wang Y, Zhang Q, Cao Y, Dai Y, Ma C, Zheng X, Ge K, Zhang H, et al. Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target. International Journal of Molecular Sciences. 2025; 26(20):9920. https://doi.org/10.3390/ijms26209920

Chicago/Turabian Style

Qin, Ruihao, Menglei Hua, Yaru Wang, Qi Zhang, Yong Cao, Yanyan Dai, Chenjing Ma, Xiaohan Zheng, Kaiyuan Ge, Huimin Zhang, and et al. 2025. "Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target" International Journal of Molecular Sciences 26, no. 20: 9920. https://doi.org/10.3390/ijms26209920

APA Style

Qin, R., Hua, M., Wang, Y., Zhang, Q., Cao, Y., Dai, Y., Ma, C., Zheng, X., Ge, K., Zhang, H., Li, S., Liu, Y., Cao, L., & Wang, L. (2025). Multiomics Investigation of Exhausted T Cells in Glioblastoma Tumor Microenvironment: CCL5 as a Prognostic and Therapeutic Target. International Journal of Molecular Sciences, 26(20), 9920. https://doi.org/10.3390/ijms26209920

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