Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer
Abstract
1. Introduction
2. TILs
2.1. T Lymphocytes
2.1.1. CD8+ T Cells
The Link Between Tumor-Elicited Immunosuppression and CTLs
2.1.2. CD4+ T Cells
2.2. B Lymphocytes
2.2.1. Regulatory B Cells (Bregs)
2.2.2. Tertiary Lymphoid Structures (TLSs)
2.3. NK Cells
3. TAMs
4. PD-1, PD-L1, and PD-L2
5. Siglec-15
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
A2AR—Adenosine A2A Receptor |
APC—Antigen Presenting Cell |
ARID1A—AT-rich Interactive Domain-containing protein 1A |
Bregs—B Regulatory Cells |
CAR NK—Chimeric Antigen Receptor Natural killer cells |
CIN—Chromosomal Instability |
CTLs—Cytotoxic T Lymphocytes |
CXCL9, CXCL10, and CXCL11—C-X-C Motif Chemokine Ligand 9, 10, and 11 |
CXCR3—C-X-C Motif Chemokine Receptor 3 |
DAP12—DNAX-Activation Protein of 12 kDa |
DCs—Dendritic Cells |
DNA—Deoxyribonucleic Acid |
EBV—Epstein–Barr Virus |
EGFR—epidermal growth factor receptor |
Fas/FasL—Fas/Fas Ligand |
FDC—follicular dendritic cell |
FOXP3—Forkhead Box Protein P3 |
GC—Gastric Cancer |
GS—Genomic Stable |
H. pylori—Helicobacter pylori |
HER-2—Human Epidermal Growth Factor Receptor 2 |
HLA—Human Leucocyte Antigen |
IFN-γ—Interferon-gamma |
Ig—Immunoglobulin |
IL-10—Interleukin-10 |
IL-17—interleukin-17 |
IL-21—interleukin-21 |
IL-6—Interleukin-6 |
IL-8—Interleukin-8 |
JAK/STAT3—Janus Kinase/Signal Transducer and Activator of Transcription 3 |
mAbs—monoclonal antibodies |
MDSCs—Myeloid-Derived Suppressor Cells |
MHC—major histocompatibility complex |
MMR—Mismatch Repair |
MSI—Microsatellite Instability |
NF-κB/NFAT—Nuclear Factor kappa-light-chain-enhancer of activated B cells/Nuclear Factor of Activated T-cells |
NK—Natural Killer |
NKG2D—Natural Killer Group 2 Member D |
NSCLC—non-small cell lung cancer |
PD-1—Programmed Cell Death-Protein-1 receptor |
PD-L1—Programmed Cell Death Ligand-1 |
PD-L2—Programmed Cell Death Ligand-2 |
PGE2—Prostaglandin E2 |
PI3K-AKT—Phosphoinositide 3-Kinase-Protein Kinase B |
RA—Rheumatoid Arthritis |
Sialyl-Tn—Sialylated Tn Antigen |
Siglec-15—Sialic Acid-Binding Immunoglobulin-Like Lectin 15 |
TAMs—Tumor-Associated Macrophages |
TCR—T Cell Receptor |
TGF-β—Transforming Growth Factor-beta |
Th—T helper |
TILs—Tumor-Infiltrating Lymphocytes |
TLSs—Tertiary lymphoid structures |
TME—Tumor Microenvironment |
TNF-α—Tumor Necrosis Factor-alpha |
Tregs—Regulatory T Cells |
TRM—Tissue-Resident Memory |
VEGF—Vascular Endothelial Growth Factor |
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Characteristics | EBV-Positive GC | MSI GC | GS GC | CIN GC |
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Molecular Features |
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Immune Cell Infiltration |
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Immunotherapy Response |
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Characteristic | Observation |
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Expression Levels |
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TME | |
Prognostic Significance | |
Immune Cell Infiltration | |
Immunotherapy Response |
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Cozac-Szőke, A.-R.; Cozac, D.A.; Negovan, A.; Tinca, A.C.; Vilaia, A.; Cocuz, I.-G.; Sabău, A.H.; Niculescu, R.; Chiorean, D.M.; Tomuț, A.N.; et al. Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer. Int. J. Mol. Sci. 2025, 26, 1156. https://doi.org/10.3390/ijms26031156
Cozac-Szőke A-R, Cozac DA, Negovan A, Tinca AC, Vilaia A, Cocuz I-G, Sabău AH, Niculescu R, Chiorean DM, Tomuț AN, et al. Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer. International Journal of Molecular Sciences. 2025; 26(3):1156. https://doi.org/10.3390/ijms26031156
Chicago/Turabian StyleCozac-Szőke, Andreea-Raluca, Dan Alexandru Cozac, Anca Negovan, Andreea Cătălina Tinca, Alexandra Vilaia, Iuliu-Gabriel Cocuz, Adrian Horațiu Sabău, Raluca Niculescu, Diana Maria Chiorean, Alexandru Nicușor Tomuț, and et al. 2025. "Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer" International Journal of Molecular Sciences 26, no. 3: 1156. https://doi.org/10.3390/ijms26031156
APA StyleCozac-Szőke, A.-R., Cozac, D. A., Negovan, A., Tinca, A. C., Vilaia, A., Cocuz, I.-G., Sabău, A. H., Niculescu, R., Chiorean, D. M., Tomuț, A. N., & Cotoi, O. S. (2025). Immune Cell Interactions and Immune Checkpoints in the Tumor Microenvironment of Gastric Cancer. International Journal of Molecular Sciences, 26(3), 1156. https://doi.org/10.3390/ijms26031156