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Regulatory B-cell states in NSCLC immunotherapy resistance: mechanisms, spatial context and translational

Xin Wang1,2, Xi Li1,3, Jing Zhou1,2

  • 1School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, China.

Cancer Immunology, Immunotherapy : CII
|June 26, 2026
PubMed

Insights

Regulatory B cells (Bregs) in non-small cell lung cancer (NSCLC) may amplify immunotherapy resistance. Understanding these inducible Bregs and their tumor microenvironment interactions is key to overcoming resistance to immune checkpoint inhibitors (ICIs).

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Non-small cell lung cancer (NSCLC) is a major cause of cancer mortality globally.
  • Immune checkpoint inhibitors (ICIs) have improved outcomes but face resistance.
  • Current resistance models focus on T cells, overlooking B cell roles.

Purpose of the Study:

  • To propose regulatory B cells (Bregs) as inducible states, not fixed lineages, in NSCLC.
  • To explore how Bregs contribute to immunotherapy resistance in NSCLC.
  • To reframe resistance mechanisms beyond T cell-centric models.

Main Methods:

  • Literature review and synthesis of current research on B cells and immunotherapy resistance.
  • Analysis of the role of tumor microenvironment and spatial context (e.g., tertiary lymphoid structures) in Breg function.
  • Examination of Breg interactions with other immunosuppressive cells.

Main Results:

  • Breg-associated states in NSCLC are inducible and influenced by tumor conditions and spatial context.
  • These Breg states can amplify resistance to ICIs by restraining anti-tumor immunity.
  • Bregs interact with other immunosuppressive populations within the tumor microenvironment.

Conclusions:

  • Regulatory B cells (Bregs) represent inducible states that contribute to immunotherapy resistance in NSCLC.
  • Understanding Breg dynamics and tumor microenvironment interactions is crucial for developing new therapeutic strategies.
  • Future strategies should be biomarker-guided, functionally selective, and spatially informed to overcome resistance.
Keywords:
Immune checkpoint inhibitorsImmunotherapy resistanceNon-small cell lung cancerRegulatory B cellsTertiary lymphoid structuresTumour microenvironment

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