Combining immunotherapy with chemoradiotherapy for advanced esophageal cancer

Inclusion Criteria:

1. Histologically-confirmed esophageal squamous cell carcinoma and whose tissue samples were taken before treatment;
2. Tumors of the esophagus are located in the thoracic cavity;
3. Pre-treatment stage as clinical II-III (AJCC/UICC 8th Edition)
4. Age is between 18 years and 75 years;
5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and expected survival time ≥12 months;
6. Adequate cardiac function. All patients should perform ECG, and those with a cardiac history or ECG abnormality should perform echocardiography with the left ventricular ejection fraction \> 50 %;
7. Adequate respiratory function with FEV1≥1.2L, FEV1%≥50% and DLCO≥50% shown in pulmonary function tests ;
8. Adequate bone marrow function (White Blood Cells \>4x10\^9 /L; Neutrophil \>2.0×10\^9 /L; Hemoglobin \> 90 g/L; platelets\>100x10\^9 /L);
9. Adequate liver function (Total bilirubin \<1.5x Upper Level of Normal (ULN); Aspartate transaminase(AST) and Alanine transaminase (ALT) \<1.5x ULN);
10. Adequate renal function (Glomerular filtration rate (CCr) \>60 ml/min; serum creatinine (SCr) ≤120 µmol/L);
11. The patient has provided written informed consent and is able to understand and comply with the study;

Exclusion Criteria:

Exclusion Criteria associated with Cancer:

1. Patients with histological non-squamous cell carcinoma;
2. Patients with advanced non-operable or metastatic esophageal cancer;
3. Pre-treatment stage as cM+, cN3 or cT4b(non-curatively-resectable verified by the local surgical investigator, AJCC/UICC 8th Edition) or cTis-1a, cT1bN0;
4. Patients with another previous or current malignant disease which is likely to interfere with treatment or the assessment of response in the judgement of the local surgical investigator;
5. Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy;

   Other Exclusion Criteria:
6. Patients with autoimmune diseases history;
7. Recently or currently taking Glucocorticoids or Immunosuppressants;
8. Patients who underwent immunotherapy in the past;
9. Allergy to any antibody drugs or allergy to Paclitaxel and Carboplatin.
10. Past or currently suffering from chronic or recurrent autoimmune diseases;
11. Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive;
12. Patients with organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation);
13. Patients with severe systematic intercurrent disease, such as active infection or poorly controlled diabetes; coagulation disorders; hemorrhagic tendency or under treatment of thrombolysis or anticoagulant therapy;
14. Any patient with a significant medical condition which is thought unlikely to tolerate the therapies. Such as cardiac disease (e.g. symptomatic coronary artery disease or myocardial infarction within last 12 months), clinically-significant lung disease, clinically-significant bone marrow, liver, renal function disorder;
15. Pregnant or lactating women and fertile women who will not be using contraception during the trial;
16. Participation in another intervention clinical trial with interference to the chemotherapeutic or chemoradiotherapeutic intervention during this study or during the last 30 days prior to informed consent;
17. Expected lack of compliance with the protocol.