Deciphering the role of QPCTL in glioma progression and cancer immunotherapy

Yu'e Liu; Shaojuan Lu; Yihong Sun; Fei Wang; Shibo Yu; Xi Chen; Lei-Lei Wu; Hui Yang; Yufeng Shi; Kaijun Zhao

doi:10.3389/fimmu.2023.1166377

Deciphering the role of QPCTL in glioma progression and cancer immunotherapy

Front Immunol. 2023 Mar 29:14:1166377. doi: 10.3389/fimmu.2023.1166377. eCollection 2023.

Authors

Yu'e Liu¹, Shaojuan Lu¹, Yihong Sun¹, Fei Wang², Shibo Yu³, Xi Chen⁴, Lei-Lei Wu⁵, Hui Yang^{6

7}, Yufeng Shi⁸, Kaijun Zhao¹

Affiliations

¹ Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
² Shanghai Pudong Hospital, Pudong Medical Center, Fudan University, Shanghai, China.
³ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
⁴ Department of Pediatrics, Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, United States.
⁵ Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
⁶ Department of Neurosurgery, National Center for Neurological Disorders, Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Huashan Hospital, Fudan University, Shanghai, China.
⁷ State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute for Translational Brain Research, Fudan University, Shanghai, China.
⁸ Tongji University Cancer Center, Shanghai Tenth People's Hospital of Tongji University, Clinical Center for Brain and Spinal Cord Research, School of Medicine, Tongji University, Shanghai, China.

Abstract

Background: Glioma is the most lethal and most aggressive brain cancer, and currently there is no effective treatment. Cancer immunotherapy is an advanced therapy by manipulating immune cells to attack cancer cells and it has been studied a lot in glioma treatment. Targeting the immune checkpoint CD47 or blocking the CD47-SIRPα axis can effectively eliminate glioma cancer cells but also brings side effects such as anemia. Glutaminyl-peptide cyclotransferase-like protein (QPCTL) catalyzes the pyroglutamylation of CD47 and is crucial for the binding between CD47 and SIRPα. Further study found that loss of intracellular QPCTL limits chemokine function and reshapes myeloid infiltration to augment tumor immunity. However, the role of QPCTL in glioma and the relationship between its expression and clinical outcomes remains unclear. Deciphering the role of QPCTL in glioma will provide a promising therapy for glioma cancer immunotherapy.

Methods: QPCTL expression in glioma tissues and normal adjacent tissues was primarily analyzed in The Cancer Genome Atlas (TCGA) database, and further validated in another independent cohort from the Gene Expression Omnibus (GEO) database, Chinese Glioma Genome Atlas (CGGA), and Human Protein Atlas (HPA). The relationships between QPCTL expression and clinicopathologic parameters and overall survival (OS) were assessed using multivariate methods and Kaplan-Meier survival curves. And the proteins network with which QPCTL interacted was built using the online STRING website. Meanwhile, we use Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases to investigate the relationships between QPCTL expression and infiltrated immune cells and their corresponding gene marker sets. We analyzed the Differentially Expressed Genes (DEGs) including GO/KEGG and Gene Set Enrichment Analysis (GSEA) based on QPCTL-high and -low expression tumors.

Results: In contrast to normal tissue, QPCTL expression was higher in glioma tumor tissue (p < 0.05). Higher QPCTL expression was closely associated with high-grade malignancy and advanced tumor stage. Univariate and multivariate analysis indicated the overall survival of glioma patients with higher QPCTL expression is shorter than those with lower QPCTL expression (p < 0.05). Glioma with QPCTL deficiency presented the paucity of infiltrated immune cells and their matching marker sets. Moreover, QPCTL is essential for glioma cell proliferation and tumor growth and is a positive correlation with glioma cell stemness.

Conclusion: High QPCTL expression predicts high grades of gliomas and poor prognosis with impaired infiltration of adaptive immune cells in the tumor microenvironment as well as higher cancer stemness. Moreover, targeting QPCTL will be a promising immunotherapy in glioma cancer treatment.

Keywords: QPCTL; biomarker; cancer immunotherapy; glioma; immune infiltration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain Neoplasms* / genetics
Brain Neoplasms* / therapy
CD47 Antigen
Drug-Related Side Effects and Adverse Reactions*
Glioma* / genetics
Glioma* / therapy
Humans
Immunotherapy
Tumor Microenvironment

Substances

CD47 Antigen

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (82073274, YFS) and the Science Technology Commission of Shanghai Municipality (20S11900700, YFS). This study was also funded by Discipline Climbing Scheme (2019YXK030) and Neuroscience Innovation and Development Research Project (YXJL-2022-00351-0183) held by KZ.