Tumor Microenvironment Changes After Neoadjuvant Chemo-Immunotherapy in Esophageal Squamous Cell Carcinoma (TME-ESCC)

March 16, 2026 updated by: Zhiyun Xu, Nanjing Medical University

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

12

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

This study will enroll adults with pathologically confirmed, potentially resectable esophageal squamous cell carcinoma who are scheduled to receive standard neoadjuvant chemotherapy combined with immunotherapy followed by surgery. Participants will be recruited from routine clinical practice at a single center. Tumor tissue will be collected before treatment and again at the time of surgical resection, and peripheral blood samples may also be collected when feasible for translational analyses of tumor microenvironment changes associated with pathological response and clinical outcomes.

Description

Inclusion Criteria:

Age 18 to 80 years; Pathologically confirmed esophageal squamous cell carcinoma; Potentially resectable disease and planned to receive standard neoadjuvant chemotherapy combined with immunotherapy followed by surgery; ECOG performance status 0 to 2; Adequate major organ function as judged by the investigator; Willing to provide tumor tissue samples at baseline and at the time of surgery; peripheral blood samples may also be collected when feasible; Written informed consent provided;

Exclusion Criteria:

Prior treatment with immune checkpoint inhibitors; Active infection, immunodeficiency, or autoimmune disease requiring systemic immunosuppressive therapy; Pregnancy or breastfeeding; Contraindications to study-related tissue sampling or planned surgery; Inability to comply with study procedures or follow-up;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
ESCC Patients Receiving Neoadjuvant Chemo-Immunotherapy
Patients with pathologically confirmed esophageal squamous cell carcinoma who are scheduled to receive standard neoadjuvant chemotherapy combined with immunotherapy followed by surgical resection. Tumor tissue samples will be collected before treatment and at the time of surgery for translational analyses of tumor microenvironment changes associated with treatment response.
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.
Other Names:
  • Biospecimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Major Pathological Response Rate
Time Frame: At surgery
Major pathological response rate, defined as the proportion of participants with 10 percent or less residual viable tumor in the resected primary tumor specimen after neoadjuvant chemo-immunotherapy.
At surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological Complete Response Rate
Time Frame: At surgery
Pathological complete response rate, defined as the proportion of participants with no residual viable tumor identified in the resected primary tumor specimen and sampled regional lymph nodes after neoadjuvant chemo-immunotherapy.
At surgery
Event-Free Survival
Time Frame: Up to 36 months
Event-free survival, defined as the time from treatment initiation to disease progression preventing surgery, postoperative recurrence, or death from any cause.
Up to 36 months
Change in Proportion of CD8-positive T Cells in Tumor Tissue
Time Frame: Baseline (before treatment) and at surgery
Change in the proportion of CD8-positive T cells among total cells in paired tumor tissue samples collected before treatment and at the time of surgical resection, assessed by single-cell RNA sequencing.
Baseline (before treatment) and at surgery
Change in T-cell Exhaustion Signature Score
Time Frame: Baseline (before treatment) and at surgery
Change in the predefined T-cell exhaustion gene signature score in paired tumor tissue samples collected before treatment and at the time of surgical resection, assessed by single-cell RNA sequencing.
Baseline (before treatment) and at surgery
Change in Spatial Immune Cell Proximity Score
Time Frame: Baseline (before treatment) and at surgery
Change in a predefined spatial immune cell proximity score in paired tumor tissue samples collected before treatment and at the time of surgical resection, assessed by spatial transcriptomics.
Baseline (before treatment) and at surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

March 10, 2026

First Submitted That Met QC Criteria

March 16, 2026

First Posted (Actual)

March 19, 2026

Study Record Updates

Last Update Posted (Actual)

March 19, 2026

Last Update Submitted That Met QC Criteria

March 16, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KY-2025-256-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared. This is a single-center exploratory study with a small sample size, and no formal external data-sharing plan has been established at the time of registration.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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