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Published on: February 12, 2017
Decoding B-cell Signatures of Complete Pathologic Response to Perioperative Chemoimmunotherapy in Non-Small Cell Lung
Belén Sierra-Rodero1, Ángeles Gil-González1, Marta Molina-Alejandre1
1Medical Oncology, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana (IDIPHISA), Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
Patients with complete pathological response (CPR) after chemoimmunotherapy (ChIO) for non-small cell lung cancer (NSCLC) show a pre-existing, mature B cell response. B cell receptor (BCR) metrics are promising biomarkers for predicting CPR.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Complete pathological response (CPR) after perioperative chemoimmunotherapy (ChIO) is linked to improved survival in resectable non-small cell lung cancer (NSCLC).
- Understanding the immune microenvironment, particularly B cells and tertiary lymphoid structures (TLS), is crucial for identifying biomarkers associated with CPR.
Purpose of the Study:
- To perform a multiomic characterization of B cells and TLS in patients with NSCLC undergoing neoadjuvant ChIO.
- To identify immune landscape features associated with achieving CPR.
Main Methods:
- Integrated analysis of B cell receptor (BCR) repertoire profiling, multiplex immunofluorescence, and bulk, spatial, and single-cell transcriptomics.
- Data collected from tumor tissue and blood of 123 patients across the NADIM/NADIM II trials at baseline, surgery, and during adjuvant therapy.
Main Results:
- CPR tumors displayed a more clonal baseline BCR repertoire, which was better maintained and enhanced during neoadjuvant ChIO.
- Blood analysis revealed CPR patients had a BCR repertoire enriched in class-switched clones with higher diversity and upregulated activation pathways.
- Neoadjuvant ChIO induced B cell-related genes in TLS, increasing TLS density at surgery; mature TLS in CPR tumors showed enriched immune activation pathways.
Conclusions:
- Patients achieving CPR possess a pre-existing, mature B cell response that is further developed by neoadjuvant ChIO.
- BCR metrics show potential as predictive biomarkers for CPR in NSCLC patients treated with perioperative ChIO.
