Circulating Immune Markers for Prognostic Evaluation in Postoperative Lung Cancer Patients

Study on the Clinical Value of Circulating Immune Markers in Prognostic Evaluation of Postoperative Lung Cancer Patients

Investigating the Clinical Value of Tumor Antigen-Specific T Cells and Immune Cell Balance in Peripheral Blood of Non-Small Cell Lung Cancer Patients for Prognostic Evaluation.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer (Diagnosis); Biomarkers / Blood
• Intervention / Treatment: Diagnostic test: Preoperative Peripheral Blood Immune Marker Analysis.

Detailed Description

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide, with surgical resection serving as the curative approach for early to intermediate stages. However, postoperative recurrence rates are high in stages IB (with high-risk features such as tumor >4 cm, poor differentiation, visceral pleural invasion, vascular invasion, or wedge resection) to IIIB, necessitating improved prognostic tools beyond TNM staging to optimize adjuvant therapies like chemotherapy or immunotherapy.

This study investigates peripheral blood immune markers as non-invasive prognostic indicators. Antigen-specific effector T cells (ETASTs) are identified via multiparametric flow cytometry, co-expressing CD137 (a T-cell activation marker) and IFN-γ (an effector cytokine) following ex vivo stimulation with tumor-associated antigens. The effector T cell to regulatory T cell ratio (Teff/Treg) reflects systemic immune homeostasis, with imbalances promoting tumor immune evasion.

Blood samples (approximately 10 mL) are collected preoperatively via venipuncture and processed within 4 hours. Peripheral blood mononuclear cells (PBMCs) are isolated using Ficoll density gradient centrifugation. For ETAST detection, PBMCs undergo stimulation with a peptide pool of common NSCLC antigens (e.g., NY-ESO-1, MAGE-A3) for 6 hours in the presence of brefeldin A, followed by intracellular staining and analysis on a BD FACSCanto II flow cytometer. Teff cells are defined as CD4+ or CD8+ T cells expressing IFN-γ, TNF-α, or IL-2; Treg cells as CD4+CD25+FoxP3+. Data acquisition targets at least 100,000 events per sample, with analysis using FlowJo software.

Follow-up includes clinical assessments every 3 months for the first 2 years, then every 6 months up to 3 years, monitoring recurrence via CT scans, PET-CT if indicated, and survival endpoints. Exploratory analyses may incorporate next-generation sequencing for driver mutations (e.g., EGFR, ALK) from tumor tissue to correlate with immune profiles.

Ethical considerations prioritize participant safety, with all procedures approved by the institutional review board. Data are de-identified and stored securely, complying with GCP standards.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Jun Zhao; Phone Number: 86-0512-67972216; Email: zhaojia0327@126.com
• Study Contact Backup: Name: Mi Liu; Phone Number: 86-0512-67972216; Email: mi.liu831116@icoud.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China
      • Soochow university, Suzhou, Jiangsu 215000
      • Contact: Jiashan Zhu; Phone Number: 86+18652808112; Email: zjs18652808112@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is a single-center, prospective, observational cohort study. The study population consists of adult patients (18-80 years) with primary non-small cell lung cancer who are scheduled for curative resection at the Thoracic Surgery Department. Eligible patients must have a postoperative pathological stage of IB (with high-risk features), IIA, IIB, or IIIB (AJCC 8th ed.), an ECOG status of 0-1, and provide informed consent. Key exclusions include prior neoadjuvant therapy, other active cancers, and significant comorbidities. A total of 200 participants are planned to be enrolled.

Description

Inclusion Criteria:

• Age 18 to 80 years.
• Diagnosed with primary non-small cell lung cancer (NSCLC) and scheduled to undergo curative lung resection at the Department of Thoracic Surgery of our institution.
• Postoperative pathological stage is IB (with tumor size >4cm or high-risk factors: poor differentiation, vascular invasion, visceral pleural invasion, sub-lobar resection, etc.), IIA, IIB, or IIIB (according to the AJCC 8th edition).
• ECOG performance status of 0 or 1.
• Voluntarily signs the informed consent form.

Exclusion Criteria:

• Received any neoadjuvant therapy prior to surgery.
• History of other active malignancies.
• Diagnosed with severe autoimmune diseases, active infections, or immunodeficiency disorders.
• Presence of severe cardiac, hepatic, or renal dysfunction.
• Pregnant or lactating women.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival	The time from the date of surgery to the first occurrence of disease recurrence, metastasis, or death from any cause.	3 years postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	The time from the date of surgery to death from any cause.	3 years postoperatively
Correlation between immune markers and clinicopathological features	To analyze the associations between preoperative levels of ETASTs, Teff/Treg ratio, and clinicopathological characteristics such as TNM stage, pathological type, and driver gene mutation status.	Baseline (preoperative)
Immunological prognostic scoring model (Nomogram)	To develop a nomogram model integrating significant immune markers (e.g., ETASTs, Teff/Treg ratio) and clinical variables (e.g., TNM stage) for predicting recurrence-free survival. The model will be internally validated using the Bootstrap method, and its discrimination (C-index) and calibration will be assessed.	3 years postoperatively

Collaborators and Investigators

• Sponsor: Zhao Jun

Study record dates

Study Major Dates

• Study Start (Estimated): December 17, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 17, 2025
• First Posted (Actual): November 21, 2025

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Prognostic Evaluation; Peripheral Blood; Tumor antigen specific T cells; Teff/Treg ratio
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Pathological Conditions, Signs and Symptoms; Lung Neoplasms; Disease
• Other Study ID Numbers: 2025979

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No