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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое 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.

Первичные конечные точки

• Major Pathological Response Rate [Срок оценки: At surgery]

Вторичные конечные точки (5)

• Pathological Complete Response Rate [Срок оценки: At surgery]
• Event-Free Survival [Срок оценки: Up to 36 months]
• Change in Proportion of CD8-positive T Cells in Tumor Tissue [Срок оценки: Baseline (before treatment) and at surgery]
• Change in T-cell Exhaustion Signature Score [Срок оценки: Baseline (before treatment) and at surgery]
• Change in Spatial Immune Cell Proximity Score [Срок оценки: Baseline (before treatment) and at surgery]

Критерии участия

Критерии включения

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;

Критерии исключения

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;

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

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• 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
• 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 Sq PMID 34519801
• 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

Идентификаторы

NCT: NCT07482774 · KY-2025-256-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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