What is the regulatory mechanism of IL-4 and its receptor in tumor immune evasion?

1. How Are Bone Marrow Immune Cells Remodeled During Tumor Immune Escape?

During tumor development and progression, significant remodeling occurs in both systemic and local immune states. Systemically, myeloid-derived bone marrow progenitor populations, immature monocytes with suppressive functions, and neutrophils are extensively mobilized into the bloodstream. Concurrently, lymphoid-derived regulatory T cells (Tregs) and regulatory B cells (Bregs) show a marked increase in peripheral frequency. Notably, Tregs undergo clonal expansion in the periphery before infiltrating tumor sites. In contrast, dendritic cells and CD8+/CD4+ T cells exhibit an overall decline in frequency, accompanied by reduced T cell receptor (TCR) diversity. Locally, within the tumor microenvironment and draining lymph nodes, immature myeloid cells accumulate while T cell populations diminish. These changes collectively indicate that promoting the generation and accumulation of immunosuppressive myeloid cells is a central strategy for tumor immune escape.

2. How Does IL-4 Signaling Drive the Generation of Pro-Tumor Myeloid Cells?

Recent studies reveal that the cytokine interleukin-4 (IL-4) and its signaling pathway play a pivotal role in this process. Single-cell transcriptomic analysis of non-small cell lung cancer models shows that IL-4 signaling is highly enriched in tumor-infiltrating monocyte-macrophage populations. Genetic experiments further confirm that specific deletion of the IL-4 receptor α subunit (IL-4Rα) in granulocyte-monocyte progenitors (GMPs) significantly inhibits lung tumor growth and reduces tumor burden. Conversely, deleting IL-4Rα in more mature monocytes or neutrophils shows no notable antitumor effects. These findings strongly suggest that IL-4 signaling's regulation of early myeloid progenitors is a critical step in generating immunosuppressive myeloid cells and promoting tumor progression.

3. What Are the Sources and Targets of IL-4 in the Bone Marrow?

A key scientific question is identifying the source of IL-4 ligands activating bone marrow IL-4 signaling in the tumor context. In-depth studies reveal that the bone marrow microenvironment itself is a significant source of IL-4, with basophils identified as the primary IL-4-producing cells. The tumor microenvironment may release soluble factors that act on the bone marrow via circulation, stimulating basophils and other type 2 immune cells to produce IL-4. Autocrine or paracrine IL-4 then acts on IL-4Rα-expressing GMPs, modulating their transcriptional programs and driving their differentiation into immunosuppressive monocytes, macrophages, and other lineages. These newly generated myeloid cells enter circulation and infiltrate tumors, contributing to a microenvironment that supports tumor growth and suppresses antitumor immunity.

4. Why Does Targeting the IL-4/IL-4Rα Axis Hold Therapeutic Potential?

The above mechanisms highlight the pivotal role of the IL-4/IL-4Rα axis in linking systemic immune alterations to local tumor immunosuppression. Blocking this pathway, particularly at the hematopoietic progenitor level, can effectively reverse the generation of immunosuppressive myeloid cells and reprogram the tumor microenvironment into a more immunogenic and antitumor-active state. This provides new combinatorial immunotherapy strategies. For example, combining IL-4 or IL-4Rα inhibitors with existing immune checkpoint blockade therapies may overcome myeloid-mediated immune resistance and improve treatment efficacy. Biomarker research (e.g., IL-4 protein levels, IL-4Rα expression profiles) will also help identify patient populations likely to benefit from such combinations.

5. How Can IL-4-Tagged Proteins Be Utilized for Research and Translation?

Accurate detection of IL-4 and its receptor is critical for basic research and clinical translation. High-specificity IL-4-tagged protein detection tools (e.g., antibody-based ELISA, flow cytometry, or immunohistochemistry) enable quantitative analysis of IL-4 expression and distribution across tissues (e.g., bone marrow, peripheral blood, tumor) and cell subsets. Comparing IL-4 dynamics in healthy individuals versus cancer patients, or pre- versus post-treatment samples, deepens understanding of its role in disease progression. Simultaneously, measuring IL-4Rα expression on target cells (e.g., GMPs) helps assess pathway activity. These protein-level data are central to validating molecular mechanisms, evaluating therapeutic strategies, and developing diagnostic and therapeutic approaches.

6. Which Vendors Provide IL-4-Tagged Proteins?

Hangzhou Start Biotech Co., Ltd. has independently developed "Human Interleukin-4 (His-tag) Recombinant Protein" (Catalog No.: S0A4021), a high-activity, high-purity, and stable cytokine product. Expressed in mammalian systems with a C-terminal His-tag, its amino acid sequence, dimeric structure, and biological functions align closely with native human IL-4. It is invaluable for Th2 immune regulation, B cell activation/isotype switching, allergy/inflammation research, and drug screening.

Technical Support: We provide comprehensive documentation, including purity/activity reports and application protocols, to accelerate research and development.

Hangzhou Start Biotech is committed to delivering high-quality reagents and solutions for global biopharma and research. For details or sample requests for "Human IL-4 (His-tag) Recombinant Protein" (Catalog No. S0A4021), please contact us.

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