Immune Responses in Brain Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 7779

Special Issue Editor

Institute of Pathology, University Hospital Salzburg, Paracelsus Medical University, Müllner Hauptstraße 48, A-5020 Salzburg, Austria
Interests: meningiomas; glioma; glioblastoma; ganglioglioma
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Special Issue Information

Dear Colleagues,

The interactions between tumor and immune response are of emerging interest in understanding both tumor biology and therapy failure. Thereby, there is a broad range of potential interactions between tumor cells and immune cells. In contrast to other organs, the brain represents a special situation: it is a site of immune privilege. However, this very traditional view has changed in recent years. Recent studies emphasize that there are complex immunological interactions between the brain and other organs. These novel developments may be of significant importance for advanced brain tumor therapy. Thereby, glioma represent the most frequent brain tumors of adults, with glioblastoma being the most malignant brain tumor, showing a devastating outcome. Despite intensive research, there are still no curative therapies available for glioma. Thus, better understanding of the complex immune–brain interactions and immune–glioma interactions may lead to new strategies in molecular glioma therapy. In this Special Issue, we aim to highlight the importance of the immune response in brain tumors with recent studies on the interaction of the immune system and brain tumors to pave the way for novel immune-modulating therapies in brain tumors. 

Dr. Theo Kraus
Guest Editor

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Keywords

  • brain tumor
  • glioma
  • glioblastoma
  • immune response
  • immune therapy
  • precision medicine

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Published Papers (3 papers)

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Research

17 pages, 4269 KiB  
Article
Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients
by Sascha Marx, Fabian Wilken, Lea Miebach, Mikael Ispirjan, Frederik Kinnen, Sebastian Paul, Sandra Bien-Möller, Eric Freund, Jörg Baldauf, Steffen Fleck, Nikolai Siebert, Holger Lode, Andreas Stahl, Bernhard H. Rauch, Stephan Singer, Christoph Ritter, Henry W. S. Schroeder and Sander Bekeschus
Cancers 2022, 14(23), 5751; https://doi.org/10.3390/cancers14235751 - 23 Nov 2022
Cited by 3 | Viewed by 3010
Abstract
Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it [...] Read more.
Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future. Full article
(This article belongs to the Special Issue Immune Responses in Brain Cancer)
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12 pages, 4439 KiB  
Article
Methylome Profiling of PD-L1-Expressing Glioblastomas Shows Enrichment of Post-Transcriptional and RNA-Associated Gene Regulation
by Georg Hutarew, Dorothee Hölzl, Tanja Schiefer, Celina K. Langwieder, Beate Alinger-Scharinger, Hans U. Schlicker, Christoph Schwartz, Karl Sotlar and Theo F. J. Kraus
Cancers 2022, 14(21), 5375; https://doi.org/10.3390/cancers14215375 - 31 Oct 2022
Cited by 2 | Viewed by 1510
Abstract
Glioblastomas are the most frequent primary brain tumors in adults. They show highly malignant behavior and devastating outcomes. Since there are still no targeted therapies available, median survival remains in the range of 12 to 15 months for glioblastoma patients. Programmed Cell Death [...] Read more.
Glioblastomas are the most frequent primary brain tumors in adults. They show highly malignant behavior and devastating outcomes. Since there are still no targeted therapies available, median survival remains in the range of 12 to 15 months for glioblastoma patients. Programmed Cell Death Ligand 1 (PD-L1) is a promising novel candidate in precision medicine. Here, we performed integrated epigenome-wide methylation profiling of 866,895 methylation-specific sites in 20 glioblastoma samples comparing PD-L1 high- (i.e., TPS (tumor proportion score) > 30%) and PD-L1 low-expressing glioblastomas (i.e., TPS < 10%). We found 12,597 significantly differentially methylated CpGs (DMCG) (Δβ ≥ 0.1 and p-value < 0.05) in PD-L1 high- compared with PD-L1 low-expressing glioblastomas. These DMCGs were annotated to 2546 tiling regions, 139 promoters, 107 genes, and 107 CpG islands. PD-L1 high-expressing glioblastomas showed hypomethylation in 68% of all DMCGs. Interestingly, the list of the top 100 significantly differentially methylated genes showed the enrichment of regulatory RNAs with 19 DMCGs in miRNA, snoRNAs, lincRNAs, and asRNAs. Gene Ontology analysis showed the enrichment of post-transcriptional and RNA-associated pathways in the hypermethylated gene regions. In summary, dissecting the methylomes depending on PD-L1 status revealed significant alterations in RNA regulation and novel molecular targets in glioblastomas. Full article
(This article belongs to the Special Issue Immune Responses in Brain Cancer)
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12 pages, 1586 KiB  
Article
Glioblastoma Embryonic-like Stem Cells Exhibit Immune-Evasive Phenotype
by Borja Sesé, Sandra Íñiguez-Muñoz, Miquel Ensenyat-Mendez, Pere Llinàs-Arias, Guillem Ramis, Javier I. J. Orozco, Silvia Fernández de Mattos, Priam Villalonga and Diego M. Marzese
Cancers 2022, 14(9), 2070; https://doi.org/10.3390/cancers14092070 - 21 Apr 2022
Cited by 6 | Viewed by 2738
Abstract
Background: Glioma stem cells (GSCs) have self-renewal and tumor-initiating capacities involved in drug resistance and immune evasion mechanisms in glioblastoma (GBM). Methods: Core-GSCs (c-GSCs) were identified by selecting cells co-expressing high levels of embryonic stem cell (ESC) markers from a single-cell RNA-seq patient-derived [...] Read more.
Background: Glioma stem cells (GSCs) have self-renewal and tumor-initiating capacities involved in drug resistance and immune evasion mechanisms in glioblastoma (GBM). Methods: Core-GSCs (c-GSCs) were identified by selecting cells co-expressing high levels of embryonic stem cell (ESC) markers from a single-cell RNA-seq patient-derived GBM dataset (n = 28). Induced c-GSCs (ic-GSCs) were generated by reprogramming GBM-derived cells (GBM-DCs) using induced pluripotent stem cell (iPSC) technology. The characterization of ic-GSCs and GBM-DCs was conducted by immunostaining, transcriptomic, and DNA methylation (DNAm) analysis. Results: We identified a GSC population (4.22% ± 0.59) exhibiting concurrent high expression of ESC markers and downregulation of immune-associated pathways, named c-GSCs. In vitro ic-GSCs presented high expression of ESC markers and downregulation of antigen presentation HLA proteins. Transcriptomic analysis revealed a strong agreement of enriched biological pathways between tumor c-GSCs and in vitro ic-GSCs (κ = 0.71). Integration of our epigenomic profiling with 833 functional ENCODE epigenetic maps identifies increased DNA methylation on HLA genes’ regulatory regions associated with polycomb repressive marks in a stem-like phenotype. Conclusions: This study unravels glioblastoma immune-evasive mechanisms involving a c-GSC population. In addition, it provides a cellular model with paired gene expression, and DNA methylation maps to explore potential therapeutic complements for GBM immunotherapy. Full article
(This article belongs to the Special Issue Immune Responses in Brain Cancer)
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