The CXCL Family Contributes to Immunosuppressive Microenvironment in Gliomas and Assists in Gliomas Chemotherapy

Abstract

Gliomas are a type of malignant central nervous system tumor with poor prognosis. Molecular biomarkers of gliomas can predict glioma patient’s clinical outcome, but their limitations are also emerging. C-X-C motif chemokine ligand family plays a critical role in shaping tumor immune landscape and modulating tumor progression, but its role in gliomas is elusive. In this work, samples of TCGA were treated as the training cohort, and as for validation cohort, two CGGA datasets, four datasets from GEO database, and our own clinical samples were enrolled. Consensus clustering analysis was first introduced to classify samples based on CXCL expression profile, and the support vector machine was applied to construct the cluster model in validation cohort based on training cohort. Next, the elastic net analysis was applied to calculate the risk score of each sample based on CXCL expression. High-risk samples associated with more malignant clinical features, worse survival outcome, and more complicated immune landscape than low-risk samples. Besides, higher immune checkpoint gene expression was also noticed in high-risk samples, suggesting CXCL may participate in tumor evasion from immune surveillance. Notably, high-risk samples also manifested higher chemotherapy resistance than low-risk samples. Therefore, we predicted potential compounds that target high-risk samples. Two novel drugs, LCL-161 and ADZ5582, were firstly identified as gliomas’ potential compounds, and five compounds from PubChem database were filtered out. Taken together, we constructed a prognostic model based on CXCL expression, and predicted that CXCL may affect tumor progression by modulating tumor immune landscape and tumor immune escape. Novel potential compounds were also proposed, which may improve malignant glioma prognosis.

Positive regulators of T cell functions as predictors of prognosis and microenvironment characteristics of low-grade gliomas

“…Thus, we can take advantage of the distinction between immunosuppressed and immune-quiet TME and perform individualized immunotherapy (30). To determine an optimal therapeutic strategy for the high-risk group, we selected rapamycin, paclitaxel, jw-7-52-1, and bortezomib for further research, all of which have been proven to be efficient in the treatment of GBM (40)(41)(42)(43). After analyzing the IC50 values of the two groups, we concluded that the patients in the high-risk group had a better response to these drugs.…”

Bioinformatics analysis of lncRNAs in the occurrence and development of osteosarcoma

“…CX3CL1 is a chemokine involved in the anti-cancer function of lymphocytes (mainly NK cells, T cells, and dendritic cells), and its increased expression in tumors can improve the prognosis of cancer patients ( 48 ). In gliomas, the CXCL family contributes to the immunosuppressive microenvironment in gliomas and enhances the sensitivity of gliomas to chemotherapy ( 49 ). The CXCL12/CXCR4 axis has become a new target for cancer therapy, and many CXCL12/CXCR4 antagonists have been developed and validated and shown promising anti-cancer activity in tumor cells ( 50 ).…”

A Lamin Family-Based Signature Predicts Prognosis and Immunotherapy Response in Hepatocellular Carcinoma

“…For example, Zhang et al estab-lished a high-precision prognostic model for predicting the clinical outcomes of lung adenocarcinoma (LUAD) patients based on TNF family genes [32]. Wang et al incorporated six CXCL family genes into a glioma prognostic model [33]. These gene family-based signatures showed excellent prognostic predictive value for the OS of patients.…”