The regulatory role of immunoglobulin-like transcript 4 in the tumor immune microenvironment

1. What are the basic structure and functions of immunoglobulin-like transcript 4 (ILT4)?

Immunoglobulin-like transcript 4 (ILT4, also known as CD85d or LILRB2) is an inhibitory receptor of the immunoglobulin superfamily, primarily expressed in myeloid cells, including monocytes, macrophages, dendritic cells, and granulocytes. This receptor binds to various ligands through its extracellular immunoglobulin-like domains, while its intracellular segment contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit phosphatases such as SHP-1 and SHP-2 to transmit inhibitory signals, thereby regulating immune cell activation and function.

ILT4 ligands include classical MHC class I molecules (HLA-A, HLA-B), non-classical MHC class I molecules (HLA-G), MHC-like molecules (CD1d), certain complement components (C4d, C3d, C4b, C3b, and iC3b), angiopoietin-like proteins, β-amyloid proteins, and semaphorin 4A. This broad ligand-binding capability enables ILT4 to play regulatory roles in various physiological and pathological processes, including pregnancy-related immune tolerance, cardiovascular disease progression, and tumor immune evasion.

2. How does ILT4 regulate immune responses in the tumor microenvironment?

In the tumor microenvironment, ILT4 expression is often upregulated, which is closely associated with its role in promoting immune suppression and helping tumors evade immune surveillance. On one hand, tumor cells or tumor-associated stromal cells can activate ILT4 on the surface of tumor-infiltrating myeloid cells by expressing ligands such as HLA-G, thereby inhibiting their antigen-presenting functions and pro-inflammatory cytokine secretion and weakening anti-tumor immune responses. On the other hand, ILT4 signaling can induce regulatory T cell expansion, suppress effector T cell function, and promote M2-type tumor-associated macrophage polarization, collectively constructing an immune-suppressive microenvironment favorable for tumor growth.

Studies have also found that ILT4 can influence tumor angiogenesis and metastasis by regulating pathways such as angiopoietin-like proteins. In various solid tumors and hematologic malignancies, high ILT4 expression is significantly correlated with tumor progression, metastasis, and poor prognosis, suggesting its potential value as a tumor biomarker and therapeutic target.

3. What role does ILT4 play in resistance to tumor immunotherapy?

With the widespread clinical application of immune checkpoint inhibitors, resistance has become an increasingly prominent issue. Research has shown that abnormal activation of the ILT4 signaling pathway is associated with resistance to PD-1/PD-L1 inhibitors. In the tumor microenvironment, ILT4 can weaken the efficacy of PD-1/PD-L1 blockade-based immunotherapy through multiple mechanisms, including inhibiting dendritic cell maturation, impairing T cell activation, and promoting the aggregation of immune-suppressive cells.

Therefore, targeting ILT4 is considered a potential strategy to overcome existing immunotherapy resistance and improve treatment response rates. Preclinical studies have demonstrated that blocking ILT4 signaling can reverse the immune-suppressive functions of tumor-associated macrophages, enhance the infiltration and activity of cytotoxic T cells, and synergize with PD-1/PD-L1 inhibitors to produce anti-tumor effects. Currently, several ILT4-targeting antibody drugs have entered preclinical or early clinical research stages, providing new directions for combination immunotherapy in tumors.

4. What is the application value of rabbit anti-human ILT4 (CD85d) antibody in tumor research?

As a research tool specifically recognizing the extracellular domain of ILT4, rabbit anti-human ILT4 (CD85d) antibody holds significant value in tumor immunology research and translational medicine. This antibody is prepared by immunizing New Zealand white rabbits and exhibits high affinity and specificity, making it suitable for various experimental platforms.

In basic research, this antibody can be used for flow cytometry to detect the proportion and phenotype of ILT4-positive immune cells in tumor tissues or peripheral blood; immunohistochemistry to analyze the spatial distribution of ILT4 in the tumor microenvironment; co-immunoprecipitation to explore interactions between ILT4 and downstream signaling molecules; and constructing ILT4-overexpressing or knockdown cell models to study its role in tumor development.

In translational research and preclinical evaluation, this antibody can be used to assess the effects of ILT4-targeting therapeutics, monitor changes in ILT4 expression in the tumor microenvironment before and after treatment, identify patient populations likely to benefit from ILT4-targeted therapy, and investigate regulatory networks between ILT4 and other immune checkpoint molecules to optimize combination therapy strategies.

5. What challenges and prospects exist for ILT4-targeted tumor therapy?

Although ILT4-targeting strategies show promising potential, they face several challenges. First, ILT4 also plays a crucial role in maintaining immune homeostasis, and complete blockade of its function may trigger autoimmune or inflammatory adverse effects, necessitating precise modulation strategies. Second, ILT4 expression patterns vary across tumor types and individuals, requiring reliable biomarker systems for patient stratification. Additionally, how to effectively combine ILT4-targeting drugs with existing immunotherapies, chemotherapies, or targeted therapies to achieve synergistic effects requires further preclinical and clinical validation.

Looking ahead, as understanding of the ILT4 signaling network and its role in tumor immunity deepens, drug development targeting this pathway will become more precise. With continuous improvements in research tools such as rabbit anti-human ILT4 (CD85d) antibodies, researchers can systematically analyze ILT4's biological functions and advance related therapeutic strategies toward clinical translation. Meanwhile, integrating multi-omics technologies and artificial intelligence analysis will help elucidate ILT4's core mechanisms in tumor immunotherapy resistance, providing scientific foundations for developing next-generation cancer immunotherapy regimens.

6. Which manufacturers provide rabbit anti-human ILT4 (CD85d) antibodies?

Hangzhou Start Biotech Co., Ltd. has independently developed the "Rabbit Anti-Human ILT4 (CD85d) Antibody" (product name: Rabbit Anti-Human ILT4 (CD85d) Antibody (S-281-50), a high-specificity, high-affinity, and highly stable immunomodulatory receptor detection tool. This product is prepared using carefully designed immunogens and rigorously validated across multiple technical platforms, including flow cytometry and immunohistochemistry, making it valuable for research on myeloid cell immune suppression, tumor microenvironment analysis, and inflammatory regulation mechanisms.

Professional Technical Support: We provide comprehensive product technical documentation, including specificity validation data, experimental protocols for various platforms, and specialized technical support to assist clients in advancing research in tumor immunology and immune regulation.

Hangzhou Start Biotech Co., Ltd. is committed to providing high-quality, high-value biological reagents and solutions for global innovative pharmaceutical companies and research institutions. For more details about the "Rabbit Anti-Human ILT4 (CD85d) Antibody" or to request sample testing, please contact us.

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