Stabilin-1 in Tumor-Associated Macrophages: A Potential Therapeutic Target in Cancer Immunotherapy
Simple Summary
Abstract
1. Introduction
2. Stabilin-1 Structure and Function
2.1. Overview of Stabilin-1 Structure
2.2. Stabilin-1: Role in Tissue Homeostasis
2.3. Stabilin-1: Role in Cancer Development and Metastasis
3. Macrophage Polarization and Tumor-Associated Macrophages (TAMs)
3.1. Macrophage Polarization
3.2. Tumor-Associated Macrophages (TAMs)
3.3. Role of STAB1 in TAMs and Immune Suppression
4. Stabilin-1: Novel Approach in Immunotherapy
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AML | Acute Myeloid Leukemia |
CAFs | Cancer-associated fibroblast |
CLEVER-1 | Common lymphatic endothelial and vascular endothelial receptor-1 |
CRC | Colorectal cancer |
CTLA4 | Cytotoxic T-lymphocyte-associated protein 4 |
EGF | Epithermal growth factors |
EVs | Extracellular vesicles |
FEEL-1 | Fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor-1 |
GDF-15 | Growth differentiation factor 15 |
HO-1 | Heme oxygenase-1 |
ICI | Immune Checkpoint Inhibitor |
KO | knockout |
LPS | Lipopolysaccharide |
LSECs | Liver sinusoidal endothelial cells |
LYVE-1 | Lymphatic vessel-specific glycoprotein |
MARCO | Macrophage receptor with collagen structure, scavenger receptor class A |
MATINS | Macrophage Antibody to FP-1305 To Inhibit Immune Suppression |
MDMs | Monocyte-derived macrophages |
MDS | Myelodysplastic syndrome |
Mrc1 | Mannose receptor C-type 1 |
PDGF | Platelet-derived growth factor |
PDEC | Patient-derived explant culture |
POSTN | Periostin |
PTC | Papillary Thyroid Carcinoma |
RELN | Reelin |
sClever1 | Soluble form of STAB1 |
siRNA | small-interfering RNA |
SI-CLP | Stabilin-1 interacting chitinase-like protein |
SPARC | Secreted protein acidic and rich in cysteine |
STAB1 | Stabilin-1 |
TAMs | Tumor-associated macrophages |
TCs | Tumor cells |
Tregs | Regulatory T cells |
TGFBi | Transforming growth factor-β-induced protein |
Th1 | T-helper-1 |
Th2 | T-helper-2 |
TNM | Tumor node metastasis |
TME | Tumor microenvironment |
TRMs | Tissue-resident macrophages |
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Cancer Type | Subjects (n) | Results | Reference |
---|---|---|---|
Bladder Cancer | 184 | Higher mortality following transurethral resection associated with STAB1+ TAM expression. | [55] |
Bladder Cancer | 68 | High STAB1+ TAMs associated with poor survival and response to neoadjuvant therapy. | [48] |
Breast Cancer | 36 | High expression of CD68+ and STAB1+ TAMs. | [68] |
Primary Invasive Breast Cancer | 148 | Infiltration of STAB1+ TAM is associated with poor survival. | [69] |
Early-stage Gastric Adenocarcinoma | 371 | High expression of STAB1+ TAMs in early-stage gastric cancer relates to poor survival rates. | [14] |
Colorectal Cancer | 159 | CD68+ and STAB1+ TAMs in peritumoral areas associated with survival of early-stage tumors. | [47] |
Colorectal Cancer | 620 | High CD68+ and STAB1+ TAMs correlated with poor survival. | [13] |
Acute Myeloid Leukemia | 87 | STAB1 expression is associated with leukocyte counts, lactate dehydrogenase levels and poor survival. | [66] |
Cancer Type | Outcomes | Reference |
---|---|---|
Lung, Breast, Lymphoma, Colon Cancer | Stabilin-1 enhances tumor growth and suppresses anti-tumor immune activity. | [50] |
Acute Myeloid Leukemia | Stabilin-1 suppresses anti-tumor activity. | [66] |
Hepatic Melanoma Metastasis | Stabilin-1 contributes to ECM modeling, immune cell infiltration, and tumor growth. | [28] |
Primary Melanoma | Reduced tumor burden with the loss of Stabilin-1. | [42] |
Papillary thyroid carcinoma | Stabilin-1 supports the seeding of tumor cells. | [70] |
Study Model | Antibody | Findings | Reference |
---|---|---|---|
Rodent | Anti-STAB1 (mouse IgG1) | Enhancement of pro-inflammatory TAMs. | [50] |
Rodent | Mouse IgG1 and anti-PD-1 (RMP1-14) | Reduction in immunosuppressive TAMs, and improved treatment efficacy in refractory tumor models. | [50] |
Rodent | Anti-mouse STAB1 (clone 1.26) | Delayed antigen degradation and shift to pro-inflammatory macrophage phenotypes. | [73] |
Clinical Trial | Humanized anti-STAB1 antibody (Bexmarilimab) | Impaired lipid metabolism in monocytes, downregulation of checkpoint inhibitors, and enhanced antigen cross-presentation. | [71] |
Clinical Trial Clinical Trial Pre-Clinical Trial | Bexmarilimab Bexmarilimab and azacitidine Bexmarilimab | Upregulation of inflammatory cascade pathways and adaptive immunity. Manageable safety profile in patients with myelodysplastic syndrome (NCT05428969). Antigen presentation; increased chemotherapy sensitivity (NCT05428969). | [12] [75] [74] |
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Gurung, J.L.; Tamang, R.L.; Madduri, L.; Bennett, R.G.; Harris, E.N.; Denton, P.W.; McVicker, B. Stabilin-1 in Tumor-Associated Macrophages: A Potential Therapeutic Target in Cancer Immunotherapy. Biology 2025, 14, 1198. https://doi.org/10.3390/biology14091198
Gurung JL, Tamang RL, Madduri L, Bennett RG, Harris EN, Denton PW, McVicker B. Stabilin-1 in Tumor-Associated Macrophages: A Potential Therapeutic Target in Cancer Immunotherapy. Biology. 2025; 14(9):1198. https://doi.org/10.3390/biology14091198
Chicago/Turabian StyleGurung, Jampa Lhamo, Raju Lama Tamang, Lepakshe Madduri, Robert G. Bennett, Edward N. Harris, Paul W. Denton, and Benita McVicker. 2025. "Stabilin-1 in Tumor-Associated Macrophages: A Potential Therapeutic Target in Cancer Immunotherapy" Biology 14, no. 9: 1198. https://doi.org/10.3390/biology14091198
APA StyleGurung, J. L., Tamang, R. L., Madduri, L., Bennett, R. G., Harris, E. N., Denton, P. W., & McVicker, B. (2025). Stabilin-1 in Tumor-Associated Macrophages: A Potential Therapeutic Target in Cancer Immunotherapy. Biology, 14(9), 1198. https://doi.org/10.3390/biology14091198