Spatiotemporal single-cell analysis reveals pre-existing follicular helper T cells in tumour-draining lymph nodes as key determinants for neoadjuvant chemoimmunotherapy response in cancer
The combination of anti-programmed cell death protein 1 (anti-PD-1) and chemotherapy has significantly improved patient survival in multiple cancer types. However, anti-PD-1 is reported to be linked with certain adverse effects and the optimal administration of anti-PD-1 is less explored. Whether anti-PD-1 added in the neoadjuvant phase can suffice beneficial response as to the long-term use remains a clinically and scientifically interesting question. Here, we conducted a phase II trial (NCT04833257) to investigate the clinical efficacy of neoadjuvant gemcitabine and cisplatin (GP) plus anti-PD-1 for only 3 cycles in nasopharyngeal carcinoma (NPC). GP plus anti-PD-1 achieved a high clinical complete response (CR) rate of 41.9% after neoadjuvant treatment and comparable 3-year survival to the long-term use of 12 cycles.
Next, we performed single-cell transcriptomic and T-cell receptor sequencing analysis on 138 samples of 49 patients, covering pre- and post-treatment paired tumour, tumour-draining lymph node (TdLN) and peripheral blood samples. Among 77 cell subpopulations we detected in the tumour microenvironment, CXCL13+CXCR5+ follicular helper T (Tfh) cells showed the highest level of correlation to favourable response.
- Data available at GSA for human and OMIX
- scRNA-seq: HRA008733, HRA008946
- Bulk RNA-seq: HRA009407
- Visium HD: HRA010609, OMIX009291
- Python v3.9.0
- Omicverse v1.5.8: https://github.com/Starlitnightly/omicverse
- scanpy v1.9.5: https://scanpy.readthedocs.io/en/stable/
- harmonypy v0.0.9: https://github.com/slowkow/harmonypy
- Lin-Quan Tang, MD, PhD, tanglq@sysucc.org.cn
- Rui-Dong Xue, PhD, rxue@hsc.pku.edu.cn