Jie Lu,1,* Zhi-Yun Zhang,2,* Sheng Zhong,1,* Davy Deng,3,* Wen-Zhuo Yang,1,* Su-Wen Wu,1 Ye Cheng,4 Yang Bai,2 Yong-Gao Mou1 

1Department of Neurosurgery/Neuro-Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Department of Plastic and Reconstructive Surgery, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA; 4Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yong-Gao Mou; Yang Bai, Email mouyg_sysucc@126.com; baiyang0221@jlu.edu.cn

Objective: Glioma is the most common primary brain tumor, with a specific immune microenvironment and aggressive nature. Novel systemic immune-inflammation indices (nSII) are the most comprehensive non-invasive biomarkers that represent patients’ peripheral immune status, which are urgently needed to improve clinical management. However, the diagnostic and prognostic value of nSII in glioma remains unknown.
Methods: From October 2006 to April 2022, 1282 patients with primary glioma were enrolled. The preoperative peripheral blood samples were collected. Correlations between novel systemic immune-inflammation indices (nSII) and glioma grades and subtypes were analyzed using ANOVA, T-test, and ordinal logistic regression. The Cox regression model, K-M survival analysis, etc. were used to study the relationship between nSII and patients’ clinical outcomes.
Results: With the higher clinical grade, the percentage of NK cells increases while Th lymphocytes and T lymphocytes decrease. The percentage of NK and Th cells was also correlated with glioma subtypes. In glioblastoma patients, the higher percentage of immunoglobulin light chains was associated with a favorable prognosis, whereas the higher percentage of B lymphocytes was associated with a poor prognosis. Our study showed high diagnostic potential, eg, combined model (C4 & NK & B cells) AUC 0.879 (grade I vs IV), combined model (Th & NK & T cells) AUC 0.845 (grade II vs IV), and combined model (C4 & NK & T cells) AUC 0.711 (grade III vs IV).
Conclusion: The nSII can serve as a robust non-invasive diagnostic and prognostic biomarker in glioma, thus promoting clinical management in screening, stratification, and treatment optimization. This study also provides a comprehensive perspective on glioma’s systemic and intracranial immune landscape, paving the way for future translational applications.

Keywords: glioma, peripheral blood, lymphocyte subsets, immunoglobulin, inflammatory cytokine