In this study, participants with locally advanced rectal cancer patients will be treated according to MMR/MSI status. There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, dMMR or MSI-H patients will receive 4 cycles of neoadjuvant Pd1 antibody Sintilimab,followed by one of the following treatments: (1) surgery and adjuvant treatment, (2）another 4 cycles of sintilimab, followed by radical surgery or observation (only for cCR) . For Cohort B, pMMR/MSS/MSI-L patients will be randomized to receive neoadjuvant chemoradiotherapy ± four cycles of Pd1 antibody Sintilimab，followed by one of the following treatments: (1) curative surgery and four cycles of adjuvant chemotherapy;(2)four cycles of chemotherapy then observation (only cCR after neoadjuvant therapy)

Inclusion Criteria:

1. Histologically proven colorectal adenocarcinoma;
2. Cohort 1: Biopsy tissues with IHC indicates deficient mismatch repair(dMMR),that is,the loss of at least one of the four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSI-H; Cohort 2: Biopsy tissues with IHC indicates proficient mismatch repair(pMMR),that is positivity of all four proteins ,MSH1,MSH2,MSH6,PMS2;or gene detection implies MSS/MSI-L
3. Clinical stage for rectal cancer patients is cT3-4N0M0 or cTxN+M0;
4. Preoperative staging methods: all patients need to accept digital rectal examination(DRE).Patients with rectal cancer undergo high-resolution MRI±ultrasound colonoscopy/transrectal ultrasound for preoperative staging. Perienteric lymph nodes with short diameter ≥10mm or the shape of lymph nodes and its MRI characteristics are consistent with typical lymph node metastasis. If endoscopic ultrasonography is used in combination, and there is a contradiction between staging methods, the data should be submitted to the evaluation team of our center for the accurate staging;
5. No symptoms of ileus; or ileus is alleviated after proximal colostomy.
6. No rectal surgery except preventative stoma;
7. No chemotherapy or radiotherapy;
8. No biotherapy (e.g.monoclonal antibodies), immunotherapy (e.g.anti-PD-1 antibody,anti-PD-L1 antibody,anti-PD-L2 antibody or CTLA-4 antibody),or other clinical trials agents;
9. No limit to previous endocrine therapy.
10. Age between 18 and 75 years;
11. ECOG performance status of 0 or 1;
12. Life expectancy: more than 2 years;
13. Hematopoietic: WBC>3×109/L;PLT>80×109/L; Hb>90g/L;
14. Hepatic: ALT and AST<2 times upper limit of normal (ULN); bilirubin<1.5 times ULN;
15. Renal: creatinine <1.5 times ULN or creatinine clearance ≥ 60 mL/min.

Exclusion Criteria:

1. Arrhythmias require antiarrhythmic therapy (with the exception of β-blockers or digoxin), symptomatic coronary artery disease or local myocardial ischemia (myocardial infarction within the past 6 months) or congestive heart failure exceeding NYHA II;
2. Severe hypertension with poor control after medication;
3. A known history of testing positive for HIV or chronic hepatitis B or C (high copy virus DNA) at active stage;
4. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening;
5. Other active severe clinical infections (NCI-CTC5.0);
6. Apparent distant metastasis away from the pelvic before surgery;
7. Cachexia, organ function decompensation;
8. Previous pelvic or abdominal radiotherapy;
9. Multiple primary colorectal cancers;
10. Epilepsy require medical treatment (such as steroid or antiepileptic therapy);
11. Other malignancy within the past 5 years with the exception of effectively treated carcinoma in situ of the cervix or basal cell carcinoma of the skin;
12. Drug abuse and medical, psychological or social factors that may interfere with patients' participation in the study or affect the evaluation of the study;
13. Patients have any active autoimmune diseases or a history of autoimmune diseases(including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis, hyperthyroidism and decreased thyroid function; patients with vitiligo or with complete remission of asthma in childhood and without any intervention in adulthood may be included; patients with asthma requiring bronchodilators intervention are not included.
14. Received any anti-infection vaccine (e.g. influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;
15. Complications require long-term treatment with immunosuppressive drugs, or requiring systemic or local use of immunosuppressive corticosteroids(>10mg/day prednisone or other therapeutic hormones);
16. Known or suspected allergy to the study drugs or to any drugs related to this trial;
17. Any unstable condition or which endangers the patients' safety and compliance;
18. Pregnant or breast-feeding women who are fertile without effective contraception;
19. Refuse to sign the informed consent.