Immune Checkpoint-Associated Locations of Diffuse Gliomas Comparing Pediatric With Adult Patients Based on Voxel-Wise Analysis

Abstract

Objective: Pediatric diffuse gliomas (pDGs) are relatively rare and molecularly distinct from pediatric pilocytic astrocytoma and adult DGs. Immunotherapy is a promising therapeutic strategy, requiring a deep understanding of tumor immune profiles. The spatial locations of brain tumors might be related to the molecular profiles. We aimed to analyze the relationship between the immune checkpoint molecules with the locations of DGs comparing pediatric with adult patients.Method: We studied 20 pDGs patients (age ≤ 21 years old), and 20 paired adult patients according to gender and histological types selected from 641 adult patients with DGs. Immune checkpoint molecules including B7-H3, CD47, and PD-L1, as well as tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), were manifested by immunohistochemical staining. Expression difference analyses and Spearman's correlation were performed. MRI data were voxel-wise normalized, segmented, and analyzed by Fisher's exact test to construct the tumor frequency and p value heatmaps. Survival analyses were conducted by Log-rank tests.Result: The median age of pediatric patients was 16 years. 55% and 30% of patients were WHO II and III grades, respectively. The left frontal lobe and right cerebellum were the statistically significant locations for pDGs, while the anterior horn of ventricles for adult DGs. A potential association between the expression of PD-L1 and TAMs was found in pDGs (p = 0.002, R = 0.670). The right posterior external capsule and the lateral side of the anterior horn of the left ventricle were predominant locations for the adult patients with high expression of B7-H3 and low expression of PD-L1 compared to pediatric ones, respectively. Pediatric patients showed significantly improved overall survival compared with adults. The prognostic roles of immune checkpoint molecules and TILs/TAMs were not significantly different between the two groups.Conclusion: Immune checkpoint-associated locations of diffuse gliomas comparing pediatric with adult patients could be helpful for the immunotherapy decisions and design of clinical trials.

An integrated biomarker of PD‐L1 expression and intraepithelial CD8+ T cell infiltration was associated with the prognosis of lung cancer patients after intracranial resection of brain metastases

“…The associations between intracranial tumor location and immune biomarkers remain unknown so far. In the present study, 89.7% of BM samples were originated from the cerebrum, especially the frontal lobe, which is consistent with the findings by Wang et al 36 Zhang et al reported that low expression of PD‐L1 may be associated with the location of primary diffuse gliomas 37 . Our results also exhibited significantly higher PD‐L1 expression on TCs in BM samples derived from the cerebrum.…”

“…In the present study, 89.7% of BM samples were originated from the cerebrum, especially the frontal lobe, which is consistent with the findings by Wang et al 36 Zhang et al reported that low expression of PD-L1 may be associated with the location of primary diffuse gliomas. 37 Our results also exhibited significantly higher PD-L1 expression on TCs in BM samples derived from the cerebrum. In addition, we found that the number and largest diameter of BM lesions were negatively correlated with the percentage of CD8 + T cells and PD-L1 expression on ICs in BM lesions.…”

GLUT1 Regulates the Tumor Immune Microenvironment and Promotes Tumor Metastasis in Pancreatic Adenocarcinoma via ncRNA-mediated Network

“…Furthermore, its expression level was remarkably correlated with the infiltration levels as well as the corresponding biomarkers of immune cells mentioned above. And the immunotherapy effect was largely affected by the expression of immune checkpoints 49 , which contributes to various prognosis 50 , 51 . In our study, GLUT1 overexpression significantly correlated with low CD8+ T-cell and CD4+ T-cell infiltration, and its expression was positively related to PD-L1 and negatively related to PD-1 in PAAD.…”