Inclusion Criteria:
* 1\) Sign written informed consent before implementing any trial related processes;
* 2\) Male or female, age ≥ 18 years;
* 3\) ECOG score 0-1;
* 4\) The primary lesion is a locally advanced rectal adenocarcinoma with histopathologically confirmed MSI-H/dMMR characteristics.;
* 5\) Combined with endoscopic ultrasonography / rectal MR scan diagnosis, patients with clinical stage t2-4a or n+m0 were evaluated for lesion resectability;
* 6\) According to the response evaluation criteria for solid tumors (RECIST version 1.1), there was at least one measurable lesion on imaging;
* 7\) The patient has not received any anti-tumor treatment in the past, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy Therapeutics et al;
* 8\) Sufficient organ function, subjects need to meet the following laboratory indicators:
1. The absolute neutrophil count (ANC)≥1.5x109/L without granulocyte colony stimulating factor in the past 14 days;
2. Platelets≥100×109/L without blood transfusion in recent 14 days;
3. Hemoglobin \>9g/dl without blood transfusion or use of erythropoietin in recent 14 days;
4. Total bilirubin ≤ 1.5×upper limit of normal (ULN);
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5×ULN;
6. Serum creatinine≤1.5×ULN and creatinine clearance (calculated by Cockcroft Gault formula)≥60ml/min;
7. Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT)≤1.5times ULN;
8. Thyroid function was normal, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
9. The myocardial enzyme spectrum is within the normal range (for example, simple laboratory abnormalities that are not clinically significant according to the comprehensive judgment of the investigator are also allowed to be enrolled).
* 9\) Female subjects of childbearing age should receive a urine or serum pregnancy test with negative results within 3 days before receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non reproductive age were defined as having been postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy;
* 10\) If there is a risk of conception, all subjects (whether male or female) need to use contraceptive measures with an annual failure rate of less than 1% during the whole treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy drug).
Exclusion Criteria:
* 1\) Diagnose distant metastasis through CT/MR/EUS;
* 2\) Other malignant tumors (excluding basal cell or squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or breast cancer) in the past 5 years;
* 3\) Severe intestinal obstruction;
* 4\) Currently participating in interventional clinical research treatment, or having received other investigational drugs or used investigational devices within 4 weeks prior to the first administration;
* 5\) Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs that stimulate or synergistically inhibit T cell receptors (such as CTLA-4, OX-40, CD137);
* 6\) Within 2 weeks before the first administration, he has received systematic systemic treatment with traditional Chinese patent medicines and simple preparations with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, interleukin, except for local use to control pleural effusion);
* 7\) An active autoimmune disease requiring systemic treatment (such as the use of disease relieving drugs, corticosteroids, or immunosuppressants) has occurred within 2 years prior to the first administration. Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatments;
* 8\) Within 7 days prior to the first administration of the study, the individual was receiving systemic corticosteroid therapy (excluding topical corticosteroids via nasal spray, inhalation, or other routes) or any other form of immunosuppressive therapy; Note: Physiological doses of glucocorticoids (≤ 10 mg/day of prednisone or equivalent) are allowed to be used;
* 9\) Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
* 10\) Individuals who are known to be allergic to the active ingredients or excipients of the investigational drug Xindilimumab, IBI310;
* 11\) Individuals with multiple factors that affect oral medication, such as inability to swallow, post gastrointestinal resection, chronic diarrhea, and intestinal obstruction;
* 12\) Not fully recovered from toxicity and/or complications caused by any intervention measures before starting treatment (i.e. ≤ grade 1 or baseline, excluding fatigue or hair loss);
* 13\) Known history of human immunodeficiency virus (HIV) infection (i.e. HIV1/2 antibody positive);
* 14\) Active hepatitis B without treatment (defined as HBsAg positive and HBV-DNA copy number detected is greater than the upper limit of normal value in the laboratory of the research center);
Note: hepatitis B patients who meet the following criteria can also be included in the group:
1. Prior to the first administration, if the HBV viral load is less than 1000 copies/ml (200 IU/ml), subjects should receive anti HBV treatment throughout the entire study chemotherapy period to avoid viral reactivation;
2. For subjects with anti HBc (+), HBsAg (-), anti HBs (-), and HBV viral load (-), prophylactic anti HBV treatment is not necessary, but close monitoring of viral reactivation is required;
3. Active HCV infected subjects (HCV antibody positive and HCV-RNA level above the detection limit);
* 15\) Vaccination with live vaccine within 30 days prior to the first administration (Day 1 of the first cycle); Note: It is allowed to receive inactivated vaccine for seasonal influenza within 30 days before the first administration; However, intranasal administration of attenuated live influenza vaccine is not allowed.
* 16\) Pregnant or lactating women;
* 17\) There are any serious or uncontrollable systemic diseases, such as:
a) Resting electrocardiogram shows significant and difficult to control abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, grade II or higher heart block, ventricular arrhythmia, or atrial fibrillation; b) Unstable angina pectoris, congestive heart failure, chronic heart failure classified as NYHA ≥ 2; c) Myocardial infarction occurred within 6 months prior to randomization; d) Poor blood pressure control (systolic blood pressure\>140 mmHg, diastolic blood pressure\>90 mmHg); e) A history of non infectious pneumonia requiring corticosteroid treatment within the year prior to the first administration, or current clinical active interstitial lung disease; f) Active pulmonary tuberculosis; g) There are active or uncontrolled infections that require systemic treatment; h) There is clinical active diverticulitis, abdominal abscess, and gastrointestinal obstruction; i) Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; j) Poor control of diabetes (FBG\>10mmol/L); k) Urine routine shows urinary protein ≥++and confirms 24-hour urinary protein quantification\>1.0 g; l) Patients with mental disorders who are unable to cooperate with treatment;
* 18\) Medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the trial results, hinder the full participation of the subjects in the study, or other situations that the researchers believe are not suitable for inclusion. The researchers believe that there are other potential risks and they are not suitable to participate in this study.
