Abstract
BackgroundNowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.MethodsThe RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.ResultsFour glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1–IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1–IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.ConclusionsANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.
Highlights
Nowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer
A list of 4,815 genes related to immunity was extracted from The Immunology Database and Analysis Portal (ImmPort, https://www.immport.org/home), which was automatically generated by searching EntrezGene and Gene Ontology (GO) terms using keywords related to immunology
To narrow down the potential genes for developing mRNA vaccine against glioma, those who serve to forecast the prognosis of glioma were further selected
Summary
Researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. Preventive and therapeutic vaccines against tumors are full of potential and attractive. These vaccines can attack and destroy malignant tumor cells that express tumor-associated antigens or tumorspecific antigens and achieve chronic therapeutic effects based on immune memory [5]. Cancer vaccines fall mainly into four categories, tumor cell, dendritic cell, DNA, and RNA types based on the antigen form [6, 7]. [2] High efficacy: In the context of clinical trial results, the mRNA vaccine is well tolerated by healthy individuals, with few side effects after eliciting a reliable immune response. MRNA sequences can be designed to encode any pathological antigen, which is conducive to individualized therapies. [3] manufactured: mRNA vaccines can be produced more rapidly under standardized processes improving responsiveness to emerging outbreaks
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