This study aimed to evaluate the safety and feasibility of neoadjuvant tislelizumab combined with chemoradiotherapy in patients with resectable esophageal squamous cell cancer. The tumor microenvironment and circulating immunological biomarkers in these patients were further evaluated to explore the factors affecting the efficacy of neoadjuvant therapy for esophageal cancer. This study will provide valuable information for further prospective clinical trials of neoadjuvant anti-PD-1 and other immunotherapy in esophageal cancer patients.

Inclusion Criteria:

1. Age 18-75
2. Histologically or cytologically confirmed resectable squamous-cell esophageal cancer ( cT1-2N+/ cT3-4aN0-3M0)
3. Eastern Cooperative Oncology Group (ECOG) status 0-1
4. Signed written informed consent prior to the implementation of any trial-related rocedures
5. Adequate organ function, evidenced by laboratory results with no contraindications to chemotherapy Absolute neutrophil count ≥ 1,500 х109/l Thrombocytes ≥ 100 х 109/l Hemoglobin ≥ 90 mg/l Creatinine ≤ 1.5 x ULN or creatinine clearance (calculated using the Cockcroft-Gault formula) ≥40 mL/min Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN) Alkaline phosphatase (ALP) > 5 x ULN Bilirubin > 1.5 х ULN

Exclusion Criteria:

1. Patients diagnosed with any other malignant tumor
2. Patients at risk for tracheoesophageal fistula or aortoesophageal fistula
3. Have received prior therapy with: chemotherapy, radiation therapy,immune checkpoint inhibitor
4. Insufficient caloric and/or fluid intake despite consultation with a dietitian and/or tube feeding
5. Have an active infection requiring systemic therapy that has not resolved 3 days (simple infection, such as cystitis) to 7 days (severe infection, such as pyelonephritis) before the first dose of trial treatment
6. Patients who cannot tolerate chemoradiotherapy or surgery due to severe cardiac, lung dysfunction
7. A history of interstitial lung disease or non-infectious pneumonia
8. Active autoimmune disease with systemic therapy (ie, use of disease modifiers, corticosteroids, or immunosuppressive drugs) in the past 2 years
9. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibody) and various viral hepatitis infections
10. Patients who have received allogeneic stem cell or solid organ transplantation
11. Women during pregnancy or lactation