Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative
Yuanyuan Zhang1, Hongyan Chen2, Hongnan Mo3
1BIOPIC, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, School of Life Sciences, International Cancer Institute, Peking University, Beijing 100871, China.
Abstract:
In triple-negative breast cancer (TNBC), the benefit of combining chemotherapy with checkpoint inhibitors is still not very clear. We utilize single-cell RNA- and ATAC-sequencing to examine the immune cell dynamics in 22 patients with advanced TNBC treated with paclitaxel or its combination with the anti-PD-L1 atezolizumab. We demonstrate that high levels of baseline CXCL13+ T cells are linked to the proinflammatory features of macrophages and can predict effective responses to the combination therapy. In responsive patients, lymphoid tissue inducer (LTi) cells, follicular B (Bfoc) cells, CXCL13+ T cells, and conventional type 1 dendritic cells (cDC1) concertedly increase following the combination therapy, but instead decrease after paclitaxel monotherapy. Our data highlight the importance of CXCL13+ T cells in effective responses to anti-PD-L1 therapies and suggest that their reduction by paclitaxel regimen may compromise the clinical outcomes of accompanying atezolizumab for TNBC treatment.
Insights
High baseline CXCL13+ T cells predict response to combination therapy in advanced triple-negative breast cancer (TNBC). Combination therapy boosts specific immune cells, unlike chemotherapy alone, highlighting CXCL13+ T cells
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- The efficacy of combining chemotherapy with checkpoint inhibitors in triple-negative breast cancer (TNBC) remains unclear.
- Understanding immune cell dynamics is crucial for optimizing TNBC treatment strategies.
Purpose of the Study:
- To investigate immune cell responses in advanced TNBC patients treated with paclitaxel or paclitaxel plus atezolizumab.
- To identify immune biomarkers predicting response to combination immunotherapy in TNBC.
Main Methods:
- Single-cell RNA sequencing and ATAC sequencing were performed on 22 advanced TNBC patients.
- Analysis focused on immune cell populations and their functional states before and after treatment.
Main Results:
- High baseline levels of CXCL13+ T cells correlated with pro-inflammatory macrophages and predicted response to combination therapy.
- Responsive patients showed increased lymphoid tissue inducer (LTi) cells, follicular B (Bfoc) cells, CXCL13+ T cells, and conventional type 1 dendritic cells (cDC1) after combination therapy.
- Paclitaxel monotherapy led to a decrease in these immune cell populations.
Conclusions:
- CXCL13+ T cells are critical for effective responses to anti-PD-L1 therapies in TNBC.
- Paclitaxel may reduce CXCL13+ T cells, potentially compromising the efficacy of concurrent atezolizumab treatment.
- Targeting or preserving CXCL13+ T cells could enhance combination immunotherapy outcomes in TNBC.
