Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery
Abstract
:1. Introduction
2. Immune Subsets in the Brain and Glioma—Summarizing the Role of the Immune System in GBM
Cytokine | Expression Inducers | Downstream Effectors | References |
---|---|---|---|
CCL2 | INF-γ IL-1 IL-4 IL-6 TGF-β TNF-α | ↑ CCR5 → ↑ ARG-1 ↑ CCR2+ TAMs ↑ CCR4+ Tregs | [64,66,67] |
CCL5 | Inherent to GBM | ↑ ARG-1 ↑ IL-10 ↑ PI3K/AKT activation ↑ mTOR activation in GSCs | [64,68,69,70,71] |
CXCL12 | TMZ Hypoxia | ↑ CD45+, CXCR4+, MMP9+ myeloid cells ↑ CXCR4+ M2 TAM | [64,72] |
IL-6 | Hypoxia Chemotherapy RT | ↑ M2 phenotype ↑ PD-L1 ↑ B7-H4 ↑ ARG-1 ↑ CD163 ↑ CD206 | [64,73,74,75] |
TGF-β | Inherent to GBM | ↓ NK infiltration ↓ CD8+ T cells ↓ CD107a ↓ INF-γ ↓ TNF-α | [64,76] |
CSF-1 | RT | ↑ M2 phenotype ↑ angiogenesis ↑ Factor H ↑ Factor H-like protein ↑ C1 inactivator ↑ CD59 ↑ CD46 ↑ CD55 | [64,77,78,79,80] |
3. Characterizing Immune Signatures in GBM
3.1. Characterizing Immunogenicity and the Immunologically “Cold Phenotype” in GBM
3.2. Characterizing the Immune Signature for Pro-Neural-to-Mesenchymal Transition (PMT)
4. Linkages Between Omic and Immune Signatures and Novel Therapies
5. Potential Therapeutic Implications and Eventual Implementation into Clinical Practice
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ARG1 | arginase-1 |
ASAH1 | N-acylsphingosine amidohydrolase 1 |
BBB | blood–brain barrier |
CAR | chimeric antigen receptor |
CCL2 | CC motif ligand 2 |
CCL5 | CC motif ligand 5 |
CCR4 | C-C chemokine receptor 4 |
CCR5 | C-C chemokine receptor 5 |
CD | cluster of differentiation |
CNS | central nervous system |
CSF | cerebrospinal fluid |
CSF1R | colony-stimulating factor 1 receptor |
CXCL12 | C-X-C motif chemokine ligand 12 |
CXCR4 | C-X-C motif chemokine receptor 4 |
DC | dendritic cell |
DNA | deoxyribonucleic acid |
EGF | epidermal growth factor |
FOXD1 | forkhead box D1 |
GBM | glioblastoma |
GPNMB | glycoprotein nmb |
GSC | glioma stem cell |
Gy | gray |
IL-1 | interleukin 1 |
IL-4 | interleukin 4 |
IL-6 | interleukin 6 |
IL-10 | interleukin 10 |
IL-13 | interleukin 13 |
INF-γ | interferon gamma |
INF-I | interferon type I |
MDSC | myeloid-derived suppressor cells |
MRI | magnetic resonance imaging |
mAb | monoclonal antibody |
mRNA | messenger RNA |
NF-κβ | nuclear factor kappa beta |
NK | natural killer |
NLR | Neutrophil-to-lymphocyte ratio |
PD-1 | programmed cell death protein 1 |
PD-L1 | programmed cell death protein ligand 1 |
PI3K | phosphoinositide 3-kinase |
PMT | proneural-to-mesenchymal transition |
RNA | ribonucleic acid |
RT | radiation therapy |
SALL1 | Sal-like 2 |
SNAI1 | snail family transcriptional repressor 1 |
STI1 | stress-inducible protein 1 |
SYNM | synemin |
TAM | tumor-associated macrophages |
TCGA | The Cancer Genome Atlas |
TGF-β | transforming growth factor β |
TIL | tumor-infiltrating lymphocytes |
TMEM119 | transmembrane protein 119 |
TME | tumor microenvironment |
TMZ | temozolomide |
TNF-α | tumor necrosis factor α |
TWIST1 | twist family bHLH transcription factor 1 |
VEGF-A | vascular endothelial growth factor A |
ZEB1 | zinc finger E-box-binding homeobox 1 |
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Jackson, L.R.; Erickson, A.; Camphausen, K.; Krauze, A.V. Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery. Curr. Oncol. 2025, 32, 16. https://doi.org/10.3390/curroncol32010016
Jackson LR, Erickson A, Camphausen K, Krauze AV. Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery. Current Oncology. 2025; 32(1):16. https://doi.org/10.3390/curroncol32010016
Chicago/Turabian StyleJackson, Luke R., Anna Erickson, Kevin Camphausen, and Andra V. Krauze. 2025. "Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery" Current Oncology 32, no. 1: 16. https://doi.org/10.3390/curroncol32010016
APA StyleJackson, L. R., Erickson, A., Camphausen, K., & Krauze, A. V. (2025). Understanding the Immune System and Biospecimen-Based Response in Glioblastoma: A Practical Guide to Utilizing Signal Redundancy for Biomarker and Immune Signature Discovery. Current Oncology, 32(1), 16. https://doi.org/10.3390/curroncol32010016