MZB1 marks a B-cell-associated stromal-immune microenvironment in cervical squamous cell carcinoma: a multi-omics...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Cervical squamous cell carcinoma (CSCC) presents a diverse tumor immune microenvironment (TIME).
• The function of MZB1, a B-cell specific molecular chaperone, in CSCC is not well understood.

Purpose of the Study:

• To investigate the role of MZB1 in CSCC and its association with the TIME and patient prognosis.

Main Methods:

• Integrative multi-omics analysis including spatial proteomics, single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomics.
• Analysis focused on malignant regions for spatial transcriptomics.

Main Results:

• MZB1 is enriched in immune-rich areas and predominantly expressed in B cells.
• MZB1-high regions showed increased infiltration of B cells, macrophages, dendritic cells, CD8+ T cells, and CD4+ T cells.
• MZB1 upregulation in tumors correlated with favorable overall survival and was associated with ECM remodeling and complement activation, despite higher T-cell dysfunction scores.

Conclusions:

• MZB1 serves as a B-cell specific marker for the stromal-immune microenvironment in CSCC.
• MZB1-high tumors exhibit immune infiltration, ECM remodeling, immune checkpoint upregulation, and a favorable prognosis.
• MZB1 may be a candidate biomarker for identifying stromal-immune tumors in CSCC, requiring clinical validation.