BTN3A: A Promising Immune Checkpoint for Cancer Prognosis and Treatment
Abstract
:1. Introduction
2. Genetic Profile and Structural Organization
3. Clinical Significance of BTN3A Molecule Expression
BTN3A Isoforms | Cancer Types | Detection Methods | Clinical Significance | Prognosis | References |
---|---|---|---|---|---|
BTN3A1 | Metastatic renal cell carcinoma (MRCC); | Baseline plasma levels of soluble BTN3A1 | Predicting PD-1(Programmed cell death protein 1) immunotherapy response | Favorable | [44] |
non-small cell lung cancer (NSCLC) | mRNA/protein expression profile | Prognostic biomarker | Favorable | [45] | |
Pancreatic ductal adenocarcinoma (PDAC) | Plasma levels of soluble BTN3A1 | Biomarkers that reflect the progression and prognosis of PDAC | Unfavorable | [22] | |
Breast cancer/non-small cell lung cancer (NSCLC) | mRNA/protein expression profile | Prognostic biomarker | Favorable | [46] | |
Low-grade glioma (LGG) | GEPIA (Gene Expression Profiling Interactive Analysis) datasets | Unfavorable | [46] | ||
Melanoma | GEPIA datasets | Favorable | [46] | ||
BTN3A2 | Pancreatic ductal adenocarcinoma (PDAC) | Transcriptional level | Prognosis marker | Unfavorable | [22] |
Epithelial ovarian cancer (EOC) | Protein expression | Prognosis marker | Favorable | [20] | |
Lung adenocarcinoma (LUAD) | mRNA/protein expression profile | Prognosis marker | Favorable | [46] | |
Pancreatic ductal adenocarcinoma | Culture cell/flow cytometry | Prognosis marker | Unfavorable | [22] | |
Breast cancer | Oncomine database | Prognosis marker | Favorable | [47] | |
Brain cancer | Oncomine database | Unfavorable | [47] | ||
BTN3A3 | Non-small cell lung cancer (NSCLC) | mRNA/protein expression profile | Prognosis marker | Favorable | [48] |
Ovarian cancer (OC) | Protein expression Cancer | Prognosis marker | Favorable | [49] | |
Gastric cancer | Therapeutics Response Portal (CTRP)/The Cancer Genome Atlas (TCGA) | Prognosis marker | Favorable | [50] |
4. BTN3A and Immune-System
4.1. BTN3A Co-Inhibitory Function
4.2. BTN3A Co-Stimulatory Function
5. BTN3A and Putative Ligand
6. BTN3A Signaling Pathways
7. Perspectives and Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
APCs | antigen-presenting cells. |
BTLA | B and T lymphocyte attenuator. |
BTN3A | butyrophilin subfamily 3 member A. |
BTNs | butyrophilins. |
c-FLIP | cellular FLICE-like inhibitory protein. |
CSC | cancer stem cell. |
CTLA-4 | cytotoxic T-lymphocyte associated protein 4. |
DAMP | damage-associated molecular patterns. |
DMAPP | dimethylallyl-pyrophosphate. |
ELISA | the enzyme-linked immunosorbent assay. |
GEPIA dataset | gene expression profiling interactive analysis. |
GZMB | granzyme B. |
HMB-PP | (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate |
ICB | immune-checkpoint blockade ICB. |
ICOS | inducible T cell co-stimulator. |
IFNγ | interferon gamma. |
JAK/STAT3 | the Janus kinase (JAK)-signal transducer and activator of transcription. |
mAb | monoclonal antibodies. |
MAPK/ERK | mitogen activated protein kinase/extracellular-signal-regulated kinase. |
MHC | major histocompatibility complex. |
NF-κB | nuclear factor kappa B. |
NK cells | natural killer cells. |
PAMPs | pathogen-associated molecular patterns. |
PBMCs | human peripheral blood mononuclear cells. |
PD-1 | programmed cell death protein 1. |
PI3K/AKT | phosphatidyl-inositol 3 kinase/serine/threonine protein kinase. |
STAT1 | signal transducer and activator of transcription. |
TBX21 | T-Box transcription factor 21. |
TCGA database | The Cancer Genome Atlas. |
TCR | T-cell receptor. |
Th1 cells | T helper 1. |
TLRs | toll-like receptors. |
TME | tumor microenvironment. |
TNBC | triple-negative breast cancer. |
TNFa | tumor necrosis factor alpha. |
TRIM | tripartite motif family protein. |
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Cell Subsets Expressing BTN3A | Detection Methods | Impact on Effector Activities | Therapeutics Potential | References |
---|---|---|---|---|
CD8 T cell | PBMCs/culture cell/flow cytometry | Attenuation of CD8 T cell proliferation and IFN production | Blocking of BTN3 signal transduction or destruction of BTN3 mRNA with small interfering RNA may be applicable for patients with tumors | [26] |
CD4 T cell | Attenuation of CD4T cell proliferation and IL-4 production | |||
Regulatory T cell | Attenuation of regulatory T cell proliferation | |||
CD4 T cell | PBMCs and lymph nodes/culture cell/flow cytometry | T-cell activation | Positive immunomodulators of T cell responses, which may ensure good responses to immunotherapies | [19] |
NK cell | Decreased IFNγ production by NK cell upon specific engagement of BTN3A2 |
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Kone, A.-s.; Ait Ssi, S.; Sahraoui, S.; Badou, A. BTN3A: A Promising Immune Checkpoint for Cancer Prognosis and Treatment. Int. J. Mol. Sci. 2022, 23, 13424. https://doi.org/10.3390/ijms232113424
Kone A-s, Ait Ssi S, Sahraoui S, Badou A. BTN3A: A Promising Immune Checkpoint for Cancer Prognosis and Treatment. International Journal of Molecular Sciences. 2022; 23(21):13424. https://doi.org/10.3390/ijms232113424
Chicago/Turabian StyleKone, Abdou-samad, Saadia Ait Ssi, Souha Sahraoui, and Abdallah Badou. 2022. "BTN3A: A Promising Immune Checkpoint for Cancer Prognosis and Treatment" International Journal of Molecular Sciences 23, no. 21: 13424. https://doi.org/10.3390/ijms232113424