Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine

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.

Clinically Explored Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma in Adults

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of the introduction of either wild-type or engineered viruses to the site of disease, where they exert an antitumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induces tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights the potential to integrate this therapeutic strategy into promising combinatory approaches.

Virus-Based Therapies for the Treatment of Recurrent High-Grade Glioma

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

Reaction of lymphoidal organs of rats on the growth of glioma C6

The study of the responce of peripheral lymphoid structures to the presence of malignant tumor in the brain offers the challenge for the use of immunotherapeutic approaches for the treatment of this disease. This work was aimed to evaluate weight indices and cellularity of lymphoid organs in rat with C6 glioma. One was found that the growth of glioma is accompanied by changes in the cellularity of the organs of the lymphatic system. The observed changes indicate the likelihood of the presentation of C6 glioma antigens in peripheral lymphoid structures, as well as the negative impact of glioma growth on thymus and spleen homeostasis.