Esophageal Squamous Cell Carcinoma
Conditions
Keywords
Tumor Microenvironment, Neoadjuvant Chemoimmunotherapy, Single-Cell RNA Sequencing, Spatial Transcriptomics, Pathological Response, Immune Escape
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.
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.
Interventions
OTHERBiological: 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.
Sponsors
Nanjing Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Spatial Immune Cell Proximity Score | 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. |
| Change in Proportion of CD8-positive T Cells in Tumor Tissue | 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. |
| Pathological Complete Response Rate | 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. |
| Event-Free Survival | 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. |
| Change in T-cell Exhaustion Signature Score | 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. |
Contacts
CONTACTZhiyun Xu, M.D.
Outcome results
None listed