The B-cell-autoantibody axis in lung cancer immunity

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Non-small cell lung cancer (NSCLC) poses a significant mortality challenge.
• Immune checkpoint inhibitors (ICIs) have improved NSCLC treatment, but resistance is common.
• Tumor-infiltrating B lymphocytes (TIL-Bs) and tertiary lymphoid structures (TLSs) are emerging prognostic factors, yet their roles are not fully understood.

Purpose of the Study:

• To synthesize current evidence on the B-cell-autoantibody axis in NSCLC.
• To explore the spatiotemporal dynamics of B-cell subsets using advanced sequencing techniques.
• To elucidate the mechanisms underlying B-cell plasticity and autoantibody functions in the tumor immune microenvironment (TIME).

Main Methods:

• Integration of single-cell RNA sequencing (scRNA-seq) data.
• Analysis of spatial transcriptomics.
• Systematic review of emerging evidence on B-cell subsets and autoantibodies in NSCLC.

Main Results:

• TLS maturation status influences TIL-B functional plasticity, with roles in both anti-tumor and pro-tumor responses.
• Autoantibodies act as active regulators within the TIME via complement activation and ADCC.
• B-cell dynamics and autoantibody functions are critical determinants of ICI resistance.

Conclusions:

• Targeting the B-cell-autoantibody axis presents a promising strategy to overcome ICI resistance in NSCLC.
• Precision immunotherapy approaches, including B-cell vaccines and TLS modulation, warrant further investigation.
• Integrating B-cell biology into NSCLC treatment paradigms is crucial for developing next-generation personalized therapies.