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

NCT07482774 | Not Yet Recruiting

• 1 other identifier: KY-2025-256-01
• Study Type: observational
• Target: 12
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Tumor Microenvironment; Neoadjuvant Chemoimmunotherapy; Single-Cell RNA Sequencing; Spatial Transcriptomics; Pathological Response; Immune Escape

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response Rate

  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 Outcomes (5)

• Pathological Complete Response Rate

  At surgery

• Event-Free Survival

  Up to 36 months

• Change in Proportion of CD8-positive T Cells in Tumor Tissue

  Baseline (before treatment) and at surgery

• Change in T-cell Exhaustion Signature Score

  Baseline (before treatment) and at surgery

• Change in Spatial Immune Cell Proximity Score

  Baseline (before treatment) and at surgery

Study Arms (1)

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

Interventions

Biological: Tumor Tissue and Blood Sample Collection OTHER

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.

Also known as: Biospecimen Collection

ESCC Patients Receiving Neoadjuvant Chemo-Immunotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Nanjing Medical University: lead

Related Publications (4)

• Stahl PL, Salmen F, Vickovic S, Lundmark A, Navarro JF, Magnusson J, Giacomello S, Asp M, Westholm JO, Huss M, Mollbrink A, Linnarsson S, Codeluppi S, Borg A, Ponten F, Costea PI, Sahlen P, Mulder J, Bergmann O, Lundeberg J, Frisen J. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science. 2016 Jul 1;353(6294):78-82. doi: 10.1126/science.aaf2403.

  PMID: 27365449 BACKGROUND

• Yang W, Xing X, Yeung SJ, Wang S, Chen W, Bao Y, Wang F, Feng S, Peng F, Wang X, Chen S, He M, Zhang N, Wang H, Zeng B, Liu Z, Kidane B, Seder CW, Koyanagi K, Shargall Y, Luo H, Peng S, Cheng C. Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for resectable esophageal squamous cell carcinoma. J Immunother Cancer. 2022 Jan;10(1):e003497. doi: 10.1136/jitc-2021-003497.

  PMID: 35022193 BACKGROUND

• Luo H, Lu J, Bai Y, Mao T, Wang J, Fan Q, Zhang Y, Zhao K, Chen Z, Gao S, Li J, Fu Z, Gu K, Liu Z, Wu L, Zhang X, Feng J, Niu Z, Ba Y, Zhang H, Liu Y, Zhang L, Min X, Huang J, Cheng Y, Wang D, Shen Y, Yang Q, Zou J, Xu RH; ESCORT-1st Investigators. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021 Sep 14;326(10):916-925. doi: 10.1001/jama.2021.12836.

  PMID: 34519801 BACKGROUND

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.

  PMID: 33538338 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Samples With DNA

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Esophageal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Central Study Contacts

Zhiyun Xu, M.D.

CONTACT

+86 15251759696; zhiyunxu2012@njmu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 10, 2026
• First Posted: March 19, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share