Downregulation of USP18 reduces tumor-infiltrating activated dendritic cells in extranodal diffuse large B cell lymphoma patients

AGING, 2021 · DOI: · Published: May 17, 2021

Cardiovascular Science Oncology Immunology

Simple Explanation

Extranodal diffuse large B-cell lymphoma (EN DLBCL) often leads to poor outcomes, and the underlying mechanism remains unclear. Immune imbalance plays an important role in lymphoma pathogenesis, suggesting that immune genes might be involved in the development of EN DLBCL. The study identified Ubiquitin-specific peptidase 18 (USP18) as a key immune gene in EN DLBCL, exhibiting low expression, regulated by LIM homeobox 2 (LHX2). The potential pathway downstream of USP18 was identified as the MAPK pathway. The study found that activated dendritic cells (aDCs) were the cell type mostly associated with USP18, indicating that USP18 participated in DC-modulating immune responses. The correlations among key biomarkers were supported by multiomics database validation.

Study Duration

Not specified

Participants

46 DLBCL patients (25 LN DLBCL, 21 EN DLBCL) from TCGA database; 16 DLBCL patients (8 LN DLBCL, 8 EN DLBCL) for IHC staining

Evidence Level

Not specified

Key Findings

1
Nine prognostic immune genes were identified in EN DLBCL, including IFNA21, KIR2DL1, MUCL1, SFTPA2, MX1, USP18, CCL1, IGLV1-36, and GLP1R.
2
USP18 was recognized as the key immune gene in EN DLBCL and was positively regulated by LHX2.
3
USP18 was positively associated with the MAPK pathway in EN DLBCL and was correlated with the immune gene set of aDCs.
4
USP18 protein expression and the number of aDCs were low in EN DLBCL tumor tissues compared to LN DLBCL.

Research Summary

This study identified nine prognostic immune genes in extranodal diffuse large B-cell lymphoma (EN DLBCL) and established a multivariate predictive model based on these genes, demonstrating that patients in the high-risk group had shorter survival times. Ubiquitin-specific peptidase 18 (USP18) was identified as a key immune gene in EN DLBCL, exhibiting low expression regulated by LIM homeobox 2 (LHX2). The MAPK pathway was identified as a potential pathway downstream of USP18. Downregulation of USP18 was associated with reduced aDC number in tumor tissues of EN DLBCL patients, indicating that targeting USP18 might serve as a promising therapy.

Practical Implications

Therapeutic Target

Targeting USP18 might serve as a promising therapy for EN DLBCL.

Prognostic Biomarker

USP18 can be used as a prognostic biomarker for EN DLBCL.

Personalized Medicine

The predictive model developed in this study can be used to identify high-risk patients who may benefit from more aggressive treatment strategies.

Study Limitations

1
The expression profiles and clinical information used here were from public databases that contain small numbers of samples, and the results were not experimentally confirmed.
2
In silico studies have some limitations.
3
The details of the regulatory relationship between LHX2 and USP18 need further experimental verification.

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