Abstract
BACKGROUND: Glioblastoma (GBM) is the most aggressive subtype of glioma with a five-year survival of 7·2 %. Immunotherapy has become a promising approach in the treatment of it. However, no improved prognosis was reached yet in phase III immunotherapy trials of glioma. Highly intertumoral heterogeneity was one of the reasons for this outcome. Hence, identifying patients who will respond to immunotherapy has become a core task in the research of GBM. In non-CNS malignancy, CD8+ tumor infiltrating lymphocytes (TILs) within tumor has been associated with response to immunotherapy and prognosis. However, no consensus was reached regarding the value of CD8+ TILs in predicting glioma patients’ response to immunotherapy. In this meta-analysis, we investigated the prognostic predictive value of infiltrating CD8+ TIL in glioma patients treated with immunotherapy. MATERIAL AND METHODS: PubMed and Web of Science were searched from 1st of January 2000 up to 15th of May 2023. Quality assessment was performed using ROBINS-I and JBI critical appraisal check list. Subgroup analyses were conducted according to clinical indicators. The protocol of the meta-analysis was registered on PROSPERO (CRD42023425790). RESULTS: A total of 8550 records were identified after the duplicates were removed, with 272 records remained for full text screening. Nine records with 187 GBM participants were included in the meta-analysis. Most of them are from Phase I or Phase II clinical trials. The immunotherapies utilized in these studies included peptide vaccination, oncolytic viral vectors therapy, DC vaccination, immune checkpoint inhibitors, and CAR-NK. Overall, no statistically significant effect of CD8+TIL infiltration was observed on overall survival (OS), progress-free survival (PFS), and survival time after immunotherapy. The subgroup analysis on peptide vaccination showed that patients with high CD8+TIL infiltration tended to have a lower OS (HR = 6·57; 95% CI: 1·12, 38·58; P = 0·037). In the subgroup analyses on male (HR = 12·34; 95% CI: 1·09, 139·18; P = 0·042) and recurrence (HR = 0·08; 95% CI: 0·01, 0·79; P = 0·030), CD8+TIL infiltration showed important effect on PFS. CONCLUSION: In general, CD8+ TIL infiltration has no prognostic predictive value in GBM patients treated with immunotherapy. However, there is predictive value for OS in the subpopulation of peptide vaccination treated GBM patients.