Longitudinal peripheral immune dynamics during anti-programmed cell death 1 neoadjuvant therapy in esophageal squamous cell carcinoma
11 affiliations
- 1School of Life Science and Technology, Jinan University, Guangzhou, China
- 2Institute of Biomedical Translational Research, Jinan University, Guangzhou, China
- 3The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China
- 4Department of Oncology, Integrated Hospital of Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou, China
- 5Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Twelfth People’s Hospital (The Affiliated Twelfth People’s Hospital of Guangzhou Medical University), Guangzhou Medical University, Guangzhou, China
- 6Guangzhou Purui Biotechnology Co., Ltd, Guangzhou, China
- 7Xinzhou District Maternal and Child Health Hospital, Wuhan, China
- 8Guangdong Provincial Key Laboratory of Spine and Spinal Cord Reconstruction, The Fifth Affiliated Hospital of Jinan University, Heyuan, China
- 9Guangzhou Twelfth People’s Hospital (The Affiliated Twelfth People’s Hospital of Guangzhou Medical University), Guangzhou Medical University, Guangzhou, China
- 10Department of VIP Inpatient and Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
- 11Department of Thoracic Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China
Abstract
Introduction: Anti-programmed cell death 1 (PD-1)-based neoadjuvant therapy is increasingly used for esophageal squamous cell carcinoma (ESCC), but paired peripheral immune dynamics and their exploratory relationship to response remain incompletely characterized.
Methods: We performed a retrospective longitudinal flow-cytometry study of 39 patients with ESCC treated with anti-PD-1-based neoadjuvant therapy, including 20 patients with paired pre-treatment and post-treatment/preoperative peripheral immune profiles. The primary paired analysis tested 75 marker-defined immune features using Wilcoxon signed-rank tests with Benjamini-Hochberg false discovery rate (FDR) correction. Exploratory extensions included response-associated changes in candidate immune features, clinical burden context, baseline-dependence, and public tissue-context bioinformatics. Public tissue data were used only as descriptive tissue context.
Results: Four features reached FDR q<0.05 in the primary paired screen: PD-1+ CD8 T cells, PD-1+ Vδ1 γδ T cells, PD-1+ Vδ2 γδ T cells, and CD19+ B cells. PD-1-defined features were interpreted as assay-defined detectable PD-1 staining readouts because therapeutic anti-PD-1 receptor occupancy or epitope masking may affect post-treatment staining. CD19+ B cells remained the non-PD-1 q<0.05 anchor in the PD-1-excluded paired sensitivity screen. In the pathology-evaluable paired cohort (n=17), no response-stratified candidate reached q<0.05; the change in NKG2D+ natural killer (NK) cells was the strongest nominal exploratory and hypothesis-generating signal.
Discussion: These data support treatment-associated marker-defined peripheral immune dynamics and generate response-linked hypotheses requiring prospective validation.
Related
- The Evolution of Neoadjuvant Treatment for Resectable Esophageal Squamous Cell Carcinoma: Past Achievements, Current Standards, and Future Perspectives
- Lymph Node Regression Improves Prognostic Stratification in Esophageal Squamous Cell Carcinoma Receiving Neoadjuvant Chemoimmunotherapy: A Multicenter Retrospective Cohort Study.
- Evaluation of the efficacy and safety of different cycles of neoadjuvant chemotherapy combined with immunotherapy in locally advanced esophageal squamous cell carcinoma: a multi-center, real-world study.
- Efficacy comparison of neoadjuvant chemotherapy, chemoradiotherapy, and chemoimmunotherapy in resectable esophageal squamous cell carcinoma: short- and long-term outcomes from a propensity score-matched analysis
- Neoadjuvant Danburstotug (IMC-001) therapy in gastric, esophageal, and hepatocellular carcinoma: the NeoChance phase II study
BibTeX
@article{li2026longitudinal,
title = {{Longitudinal peripheral immune dynamics during anti-programmed cell death 1 neoadjuvant therapy in esophageal squamous cell carcinoma}},
author = {Linpeng Li and Lingwen Meng and Xinru Chen and Jiahui Li and Pengfei Li and Bo Dong and Chengjing Huang and Wei Zhou and Nuan Li and Guodong Sun and Jiawei Li and Guojie Tan and Li Jiang and Dan Tian},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1917487},
url = {https://doi.org/10.3389/fimmu.2026.1917487},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Longitudinal peripheral immune dynamics during anti-programmed cell death 1 neoadjuvant therapy in esophageal squamous cell carcinoma
AU - Linpeng Li
AU - Lingwen Meng
AU - Xinru Chen
AU - Jiahui Li
AU - Pengfei Li
AU - Bo Dong
AU - Chengjing Huang
AU - Wei Zhou
AU - Nuan Li
AU - Guodong Sun
AU - Jiawei Li
AU - Guojie Tan
AU - Li Jiang
AU - Dan Tian
PY - 2026
DA - 2026/10/12
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1917487
UR - https://doi.org/10.3389/fimmu.2026.1917487
AB - Introduction: Anti-programmed cell death 1 (PD-1)-based neoadjuvant therapy is increasingly used for esophageal squamous cell carcinoma (ESCC), but paired peripheral immune dynamics and their exploratory relationship to response remain incompletely characterized. Methods: We performed a retrospective longitudinal flow-cytometry study of 39 patients with ESCC treated with anti-PD-1-based neoadjuvant therapy, including 20 patients with paired pre-treatment and post-treatment/preoperative peripheral immune profiles. The primary paired analysis tested 75 marker-defined immune features using Wilcoxon signed-rank tests with Benjamini-Hochberg false discovery rate (FDR) correction. Exploratory extensions included response-associated changes in candidate immune features, clinical burden context, baseline-dependence, and public tissue-context bioinformatics. Public tissue data were used only as descriptive tissue context. Results: Four features reached FDR q<0.05 in the primary paired screen: PD-1+ CD8 T cells, PD-1+ Vδ1 γδ T cells, PD-1+ Vδ2 γδ T cells, and CD19+ B cells. PD-1-defined features were interpreted as assay-defined detectable PD-1 staining readouts because therapeutic anti-PD-1 receptor occupancy or epitope masking may affect post-treatment staining. CD19+ B cells remained the non-PD-1 q<0.05 anchor in the PD-1-excluded paired sensitivity screen. In the pathology-evaluable paired cohort (n=17), no response-stratified candidate reached q<0.05; the change in NKG2D+ natural killer (NK) cells was the strongest nominal exploratory and hypothesis-generating signal. Discussion: These data support treatment-associated marker-defined peripheral immune dynamics and generate response-linked hypotheses requiring prospective validation.
SN - 1664-3224
ER -