Inclusion Criteria:
* Has signed the written informed consent form and voluntarily participates in this study;
* Aged 18-80 years, male or female;
* Histopathologically or cytologically confirmed esophageal squamous cell carcinoma;
* Clinical stage: cT1b-cT2N+M0 or cT3-cT4a any N M0;
* Has at least one measurable lesion (per RECIST Version 1.1: the measurable lesion has a longest diameter ≥10 mm on spiral CT scan, or a malignant lymph node with short-axis diameter ≥15 mm);
* Expected to achieve R0 resection;
* ECOG Performance Status (PS) 0-1 (see Appendix 1);
* Has not received any prior anti-tumor therapy for esophageal cancer, including radiotherapy, chemotherapy, surgery, etc.;
* Plans to receive surgical resection after completion of neoadjuvant therapy;
* No contraindications to surgery.
* Adequate organ function as specified below:
1. Hematology laboratory values (No blood products, hematopoietic growth factors, leukopoietic agents, thrombopoietic agents or anti-anemia medications are permitted within 14 days prior to the first study drug administration):
White blood cell count ≥ 3.0 × 10⁹/L Absolute neutrophil count ≥ 1.0 × 10⁹/L Platelet count ≥ 80 × 10⁹/L Hemoglobin ≥ 90 g/L
2. Serum chemistry:
Total bilirubin ≤ 1.5 × ULN Alanine transaminase (ALT) ≤ 2.5 × ULN; Aspartate transaminase (AST) ≤ 2.5 × ULN Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min (calculated by the Cockcroft-Gault formula, see Appendix 2)
3. Coagulation function:
International normalized ratio (INR) ≤ 1.5 × ULN Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN
* Female subjects of reproductive potential must have a negative serum or urine pregnancy test within 72 hours prior to initiation of study drug, and must use effective contraception (e.g., intrauterine device, oral contraceptives, condoms) throughout the study and for at least 3 months after the last dose of study drug. Male subjects with female partners of reproductive potential must use effective contraception throughout the study and for 3 months after the last dose.
* Subjects with good compliance and willingness to complete follow-up visits.
Exclusion Criteria:
* Tumor invades adjacent organs of the esophageal lesion (major arteries or trachea);
* Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage;
* Poor nutritional status with BMI \< 18.5 kg/m². Subjects whose nutritional status is corrected by symptomatic nutritional support prior to enrollment may be considered for inclusion upon assessment by the principal investigator;
* History of allergy to any component of monoclonal antibodies, adebrelimab, thymalfasin, paclitaxel, carboplatin or other platinum agents;
* Previously received or currently receiving any of the following treatments:
1. Any anti-tumor radiotherapy, chemotherapy, immunotherapy, targeted therapy or other anti-neoplastic agents;
2. Immunosuppressive agents or systemic corticosteroids administered for immunosuppressive purposes (prednisone \>10 mg/day or equivalent dose) within 2 weeks prior to the first study drug administration. Inhaled or topical steroids, and corticosteroid replacement therapy (prednisone \>10 mg/day or equivalent dose) are permitted in the absence of active autoimmune disease;
3. Live attenuated vaccines administered within 4 weeks prior to the first study drug administration;
4. Major surgery or severe trauma within 4 weeks prior to the first study drug administration.
* Active autoimmune disease or history of autoimmune disease, including but not limited to: interstitial pneumonia, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (subjects receiving hormone replacement therapy may be enrolled). Subjects with psoriasis or childhood asthma/allergies completely resolved without any intervention in adulthood can be considered eligible; patients requiring medical intervention with bronchodilators are excluded.
* History of immunodeficiency, including positive HIV test, other acquired or congenital immunodeficiency diseases, history of solid organ transplantation or allogeneic bone marrow transplantation;
* Poorly controlled cardiac signs or diseases, including but not limited to: (1) NYHA Class II or higher heart failure; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmia without clinical intervention or still poorly controlled after intervention.
* Severe infection (CTCAE Grade \>2) within 4 weeks before the first study drug administration, such as severe pneumonia requiring hospitalization, bacteremia, infectious complications, etc. Active pulmonary inflammation indicated by baseline chest imaging; subjects presenting with signs and symptoms of infection within 14 days before first dosing or requiring oral/intravenous antibiotics, except for prophylactic antibiotic use.
* Active pulmonary tuberculosis confirmed by medical history or CT scan; history of active pulmonary tuberculosis within 1 year before enrollment; or history of active pulmonary tuberculosis more than 1 year previously without standardized treatment.
* Hereditary bleeding diathesis or coagulation disorders. Clinically significant bleeding events or definite bleeding tendency within 3 months before enrollment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ≥++.
* Diagnosis of another malignant tumor within 5 years prior to the first study drug administration, except malignancies with low risk of metastasis or death (5-year survival rate \>90%). Fully treated basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of cervix, etc., may be considered for enrollment.
* Pregnant or breastfeeding women.
* Any other conditions judged by the investigator that may force premature study discontinuation, such as other severe diseases (including psychiatric disorders) requiring combined medication, alcohol abuse, drug abuse, family or social factors that may affect subject safety or compliance.
