Table of Contents
Introduction
BCL10, a key adapter protein, plays a critical role in the activation of the NF-κB signaling pathway, which is essential for immune response regulation. Understanding BCL10’s function in various cancer types is crucial, particularly as it interacts with immune cell dynamics within the tumor immune microenvironment (TIME). This article explores the expression of BCL10 across different cancers, its impact on immune cell infiltration, its role in T cell exhaustion, mechanisms regulating PD-1 expression, and the therapeutic implications of targeting BCL10 in cancer treatments.
BCL10 Expression in Various Cancer Types
Recent studies have highlighted the dysregulation of BCL10 across numerous cancer types, suggesting its involvement in tumorigenesis and progression. For instance, data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases indicate that BCL10 is upregulated in various malignancies, including colorectal cancer (CRC), breast cancer (BRCA), and cervical squamous cell carcinoma (CESC) (Gu et al., 2025). This widespread expression correlates with poor patient outcomes, indicating that BCL10 may serve as a potential prognostic biomarker.
| Cancer Type | BCL10 Expression Level | Prognostic Impact |
|---|---|---|
| Colorectal Cancer | High | Poor survival rates |
| Breast Cancer | High | Associated with metastasis |
| Cervical Cancer | Elevated | Correlates with T cell exhaustion |
The expression of BCL10 can provide insights into the immune landscape of tumors, guiding treatment decisions and predicting responses to therapies.
Impact of BCL10 on Immune Cell Infiltration
BCL10’s expression significantly influences the infiltration of immune cells within the TIME. In high BCL10-expressing tumors, there is a notable reduction in cytotoxic T cell (CD8+ T cells) infiltration, coupled with an increase in immunosuppressive populations such as regulatory T cells (Tregs) and CD4+ Th2 cells. Studies utilizing algorithms such as CIBERSORT and QUANTISEQ confirm that BCL10 negatively correlates with the presence of effector immune cells while positively correlating with Treg infiltration (Gu et al., 2025).
| Immune Cell Type | Correlation with BCL10 | Tumor Types |
|---|---|---|
| CD8+ T cells | Negative | CESC, COAD |
| Tregs | Positive | CESC, BRCA |
| CD4+ Th2 cells | Positive | COAD, STAD |
This suggests that BCL10 not only plays a role in tumor growth but also in shaping the immune microenvironment, leading to immune evasion.
BCL10 and T Cell Exhaustion in Tumor Immunity
T cell exhaustion is a critical phenomenon in cancer immunology, characterized by the reduced ability of T cells to proliferate and exert effector functions. Elevated levels of BCL10 within tumors have been associated with increased expression of immune checkpoint molecules such as PD-1. This relationship is particularly evident in models of CESC, where BCL10 expression is correlated with PD-1 levels on CD8+ T cells (Gu et al., 2025).
| Checkpoint Molecule | Correlation with BCL10 | Effect on T Cells |
|---|---|---|
| PD-1 | Positive | Promotes exhaustion |
| CTLA4 | Positive | Inhibits activation |
| LAG3 | Positive | Further dampens response |
The overexpression of BCL10 leads to a feedback loop, exacerbating T cell exhaustion and enabling tumor cells to evade immune detection.
Mechanisms of BCL10 in Regulating PD-1 Expression
BCL10’s role in regulating PD-1 expression is linked to its function in the NF-κB pathway. Chronic stimulation of T cells by tumor antigens leads to prolonged BCL10 activation, resulting in sustained NF-κB signaling. This process upregulates PD-1 expression, further inhibiting T cell functionality and contributing to immune evasion. Inhibition of BCL10 may, therefore, enhance T cell responses against tumors by reducing PD-1 levels, potentially reversing T cell exhaustion (Gu et al., 2025).
Therapeutic Implications of Targeting BCL10 in Cancer
Targeting BCL10 presents a promising therapeutic avenue to enhance anti-tumor immunity. Inhibition of BCL10 could potentially restore the functionality of exhausted T cells, promote their proliferation, and encourage infiltration into the tumor microenvironment. Preclinical models suggest that strategies aimed at downregulating BCL10 may improve the efficacy of existing immunotherapies, such as checkpoint inhibitors, by reactivating T cell responses (Gu et al., 2025).
Conclusion
BCL10 plays a multifaceted role in tumor biology, particularly in modulating the immune microenvironment. Its expression across various cancers is associated with immune evasion mechanisms, including T cell exhaustion and altered immune cell infiltration. Understanding the precise mechanisms underlying BCL10’s function could unveil new targets for immunotherapy, ultimately improving patient outcomes in cancer treatment.
References
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Gu, J., Chen, C., Chen, Y., Lv, W., Li, F., Zhu, P., He, P., Du, Y., Liu, H., & Zhu, B. (2025). High-expression of BCL10 inhibits cell-mediated immunity within the tumor immune microenvironment. Frontiers in Immunology, 16, 1616321. https://doi.org/10.3389/fimmu.2025.1616321
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FAQ
What is BCL10? BCL10 is a signaling molecule that plays a crucial role in the activation of the NF-κB pathway, impacting immune cell function.
How does BCL10 affect T cell exhaustion? Elevated BCL10 levels can lead to increased PD-1 expression on T cells, contributing to their exhaustion and reducing their anti-tumor activity.
Can targeting BCL10 improve cancer treatment? Yes, targeting BCL10 may enhance T cell responses and improve the efficacy of immunotherapies by reversing T cell exhaustion.
What types of cancers show dysregulation of BCL10? BCL10 is upregulated in various cancers, including colorectal cancer, breast cancer, and cervical cancer, correlating with poorer patient outcomes.
