Single-cell transcriptomics reveals tumor-infiltrating B cell function after neoadjuvant pembrolizumab and
Lingjie Hou1,2,3,4,5, Siyuan Zhang1,2,3,4,5, Wenwen Yu1,2,3,4,5
1National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, No. 45 Binshui Road, Hexi District, Tianjin 300060, China.
Abstract:
Non-small cell lung cancer (NSCLC) is the most pervasive lung cancer subtype. Recent studies have shown that immune checkpoint inhibitors achieved favorable clinical benefits in resectable NSCLC; however, the associated mechanism remains unclear. The role of T cells in antitumor immunity has received considerable attention, while the antitumor effects of tumor-infiltrating B cells (TIBs) in NSCLC remain poorly understood. Here, we conducted a single-cell RNA sequencing analysis of immune cells isolated from 12 patients with stage IIIA NSCLC to investigate B cell subtypes and their functions following neoadjuvant chemoimmunotherapy. We confirmed the simultaneous existence of the 4 B cell subtypes. Among them, memory B cells were found to be associated with a positive therapeutic effect to neoadjuvant chemoimmunotherapy. Furthermore, we found that G protein-coupled receptor 183 was most prevalent in memory B cells and associated with a positive therapeutic response. Multiplex immunofluorescence and flow cytometry experiments in an additional cohort of 22 treatment-naïve and 30 stage IIIA/IIIB NSCLC patients treated with neoadjuvant chemoimmunotherapy verified these findings. Overall, our analysis revealed the functions of TIBs and their potential effect on clinical treatment in NSCLC.
Insights
This study reveals that memory B cells and G protein-coupled receptor 183 are linked to positive outcomes in non-small cell lung cancer (NSCLC) patients receiving neoadjuvant chemoimmunotherapy.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Non-small cell lung cancer (NSCLC) is a prevalent malignancy.
- Immune checkpoint inhibitors show promise in resectable NSCLC, but mechanisms are unclear.
- The role of tumor-infiltrating B cells (TIBs) in NSCLC immunity is not well understood.
Purpose of the Study:
- To investigate B cell subtypes and their functions in NSCLC after neoadjuvant chemoimmunotherapy.
- To identify specific B cell populations associated with positive therapeutic responses.
- To explore the role of G protein-coupled receptor 183 in NSCLC immune responses.
Main Methods:
- Single-cell RNA sequencing of immune cells from 12 stage IIIA NSCLC patients.
- Analysis of B cell subtypes and their functional markers.
- Validation using multiplex immunofluorescence and flow cytometry in an additional patient cohort.
Main Results:
- Four distinct B cell subtypes were identified in NSCLC patients.
- Memory B cells correlated with a positive therapeutic effect from neoadjuvant chemoimmunotherapy.
- G protein-coupled receptor 183 was highly expressed in memory B cells and associated with favorable treatment response.
Conclusions:
- Tumor-infiltrating B cells, particularly memory B cells, play a significant role in NSCLC immunity.
- G protein-coupled receptor 183 may serve as a biomarker for predicting treatment response in NSCLC.
- Understanding TIB functions can guide future NSCLC therapeutic strategies.
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