Single-cell sequencing in diffuse large B-cell lymphoma: C1qC is a potential tumor-promoting factor

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Complement component 1q (C1q) is integral to the classical complement pathway.
• Elevated C1q expression correlates with poor prognosis in various cancers.
• The specific role of C1q in diffuse large B-cell lymphoma (DLBCL) pathogenesis remains unclear.

Purpose of the Study:

• To investigate the mechanism by which C1q promotes DLBCL.
• To identify immunocyte subgroups associated with DLBCL prognosis.
• To explore C1qC as a potential therapeutic target in DLBCL.

Main Methods:

• Multiplex immunohistochemistry (mIHC) and single-cell sequencing to analyze immunocyte populations and C1qC expression in DLBCL tissues.
• LASSO regression to construct a risk prediction model based on immunocytes.
• In vitro co-culture experiments and molecular assays (Western blot, qPCR) to assess M2 macrophage function and interactions with lymphoma cells following C1qC knockdown.
• Analysis of clinical data from DLBCL patients to evaluate the prognostic significance of C1qC+ M2 macrophages.

Main Results:

• T cell subtypes, neutrophils, and M2 macrophages were identified as prognostic factors in DLBCL.
• C1qC was identified as a key gene associated with DLBCL prognosis, with high expression observed in M2 macrophages.
• C1qC knockdown reduced M2 macrophage markers (e.g., CD163) and impaired their ability to promote lymphoma cell proliferation and reduce drug sensitivity.
• High expression of C1qC+ M2 macrophages independently predicted poor prognosis in DLBCL patients.
• Increased C1qC expression correlated with immune checkpoint activation, regulatory T cell (Treg) infiltration, and M2 macrophage abundance.

Conclusions:

• C1qC plays a significant role in DLBCL pathogenesis, primarily through its influence on M2 macrophages.
• C1qC+ M2 macrophages serve as a potential prognostic biomarker for DLBCL.
• Targeting C1qC presents a promising therapeutic avenue for DLBCL treatment.