NCT07482774

Tumor Microenvironment Changes After Neoadjuvant Chemo-Immunotherapy in Esophageal Squamous Cell Carcinoma

Dynamic Characterization of Tumor Microenvironment Remodeling and Immune Escape After Neoadjuvant Chemo-Immunotherapy in Esophageal Squamous Cell Carcinoma Using Single-Cell and Spatial Transcriptomics

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 12 (estimated)
• Sponsor: Nanjing Medical University · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This prospective observational study aims to characterize dynamic changes in the tumor microenvironment of patients with esophageal squamous cell carcinoma receiving standard neoadjuvant chemotherapy combined with immunotherapy followed by surgical resection. Paired tumor tissue samples will be collected before treatment and at surgery, and peripheral blood samples may also be collected when feasible. Single-cell RNA sequencing and spatial transcriptomics will be used to evaluate changes in cellular composition, transcriptional states, and spatial organization within the tumor microenvironment and to explore their associations with pathological response.

Detailed description

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies of the digestive tract and remains associated with poor prognosis, particularly in patients with locally advanced disease. In recent years, neoadjuvant chemotherapy combined with immune checkpoint inhibitors has emerged as a promising treatment strategy and has been increasingly adopted in clinical practice. Although encouraging pathological response rates have been reported, a substantial proportion of patients do not derive durable benefit from this treatment approach. The tumor microenvironment plays a critical role in shaping antitumor immune responses and may influence the efficacy of immunotherapy. However, the dynamic remodeling of the tumor microenvironment during neoadjuvant chemo-immunotherapy in ESCC remains incompletely understood. In particular, changes in cellular composition, transcriptional states of immune and stromal cells, and spatial interactions among different cell populations may contribute to treatment sensitivity or resistance. This prospective observational cohort study aims to investigate dynamic changes in the tumor microenvironment of ESCC patients treated with standard neoadjuvant chemotherapy combined with immunotherapy followed by surgical resection. Patients with pathologically confirmed ESCC who are scheduled to receive standard neoadjuvant chemo-immunotherapy and subsequent surgery will be enrolled. Tumor tissue samples will be collected at baseline prior to treatment and again at the time of surgical resection. Peripheral blood samples may also be collected at selected time points when feasible. Single-cell RNA sequencing will be used to characterize the cellular heterogeneity and transcriptional states of tumor, immune, and stromal cells within the tumor microenvironment. Spatial transcriptomics will be used to evaluate the spatial organization and interactions among different cell populations within tumor tissues. The study will compare molecular and cellular features between patients who achieve pathological complete response or major pathological response and those who do not achieve significant pathological response. These analyses are intended to identify potential mechanisms of immune escape and to explore biomarkers associated with response to neoadjuvant chemo-immunotherapy. Exploratory analyses may also evaluate associations between tumor microenvironment features and clinical outcomes, including event-free survival. The results of this study may improve understanding of the biological mechanisms underlying response and resistance to neoadjuvant chemo-immunotherapy in ESCC and may provide a basis for future translational and therapeutic studies.

Conditions

• Esophageal Squamous Cell Carcinoma

Interventions

Type	Name	Description
OTHER	Biological: Tumor Tissue and Blood Sample Collection	Tumor tissue samples will be collected at baseline before treatment and again at the time of surgical resection. Peripheral blood samples may also be collected when feasible. Collected biospecimens will be used for single-cell RNA sequencing, spatial transcriptomics, and related molecular analyses to evaluate dynamic changes in the tumor microenvironment associated with treatment response.

Timeline

• Start date: 2026-06-01
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2026-03-19
• Last updated: 2026-03-19