The goal of this clinical trial is to learn if immune microenvironment modification could improve the effect of chemoradiotherapy for patients with local advanced esophageal squamous cell carcinoma. The main questions it aims to answer are:

1. Does immune microenvironment could be modified by medium dose of three drugs (paclitaxel, cisplatin, 5-FU), PD1 checkpoint inhibitor, probiotics, and thymosin α1？
2. Does induction and consolidation of PD1 checkpoint inhibitor improve the effect of chemoradiotherapy for patients with esophageal cancer?

This is a single arm study. Participants will:

1. Take one cycle of induction chemotherapy (paclitaxel, cisplatin, 5-FU) and immunotherapy (Sintilimab), two cycle of concurrent chemoradiotherapy, one cycle of consolidation chemo-immunotherapy, and then 1 year of immunotherapy.
2. Take probiotics (Clostridium Butyricum) for 1 year and thymosin alpha-1 daily during radiotherapy.

Concurrent chemoradiotherapy is the standard treatment for patients with inoperable local advanced esophageal squamous cell carcinoma. However, over half of patients will relapse. How to improve effects? We focus on tumor microenvironment transformation by three drug chemotherapy, PD1 inhibitor, probiotics, and thymosin α1，and intent to improve radiosensitivity and reduce recurrence.

Inclusion Criteria:

1. Sign written informed consent before implementing any trial related procedures;
2. Age range from 18 to 80 years old;
3. Stage II-III and stage IV esophageal squamous cell carcinoma with only extraregional lymph node metastasis determined by histopathology;
4. Inability to undergo surgical resection or patient refusal to undergo surgery;
5. ECOG PS 0-1;
6. Expected survival time>3 months;
7. Sufficient organ function is required for the subject to meet laboratory indicators

Exclusion Criteria:

1. After esophageal or tracheal stent implantation surgery;
2. Due to the obvious invasion of tumors into adjacent organs (arteries or trachea) of the esophageal lesion, there is a higher risk of Patients at risk of bleeding or perforation, or those who have formed fistulas;
3. Diagnosed as malignant diseases other than esophageal cancer within 3 years prior to initial administration (excluding those that have undergone curative treatment)
4. Currently participating in intervention clinical research treatment, or having received other treatments within 4 weeks prior to initial administration Researching drugs or using research instruments for treatment;
5. Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or targeting another stimulus or synergistic inhibition of T cell receptors (such as CTLA-4, OX-40, CD137) Medications;