Clinical Research Directory

Inclusion Criteria: * Histological identified colon and upper rectum adenocarcinoma, Tumor biopsy immunohistochemical (IHC) identified pMMR, including all of the MSH1,MSH2,MSH6 and PMS2 protein expression and diagnosed as proficient mismatch repair(pMMR), or next generation sequencing identified (MSS)； MRI identified tumor inferior margin higher than peritoneal reflection, * Clinical staging T4NxM0, with or without positive MRF, with or without positive EMVI, * Staging method：all patients undergo chest,abdominal and pelvic enhanced CT, rectal palpation, high resolution MRI examination，positive perienteric lymph node(LN): short diameter ≥10mm LN or LN with typical metastatic shape and MRI character, clinical data should be re-evaluated and judged by center evaluation group when there are contradictory stagings，distant metastasis were excluded by chest and abdominal enhanced CT and pelvic enhanced MRI, * No intestinal obstruction symptom，or obstruction relieved after proximal colostomy, * No rectal surgery history, * No chemotherapy or radiotherapy history, * No biopharmaceutical treatment history(such as monoclonal antibody), immunotherapy(such as anti PD-1antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4), or other research drug treatment, * Endocrinotherapy history restriction:No * informed consent assigned, Exclusion Criteria: * Arrhythmia need anti-arrhythmia treatment(except β-blocking agent or Digoxin)，symptomatic coronary heart disease or myocardial ischemia(myocardial infarction within 6 months) or congestive heart-failure (CHF) \> NYHA grade II, * Severe hypertension not well controlled by drugs, * HIV infection history or active phase of chronic Hepatitis B or C(high copies of virus DNA), * Active tuberculosis(TB)，accepting anti-TB treatment or anti-TB treatment within 1 year before trial screen, * Other active clinical severe infection(NCI-CTC V5.0), * Outside pelvic distant metastasis evidences, * Dyscrasia, organ dysfunction, * Pelvic or abdominal radiotherapy history, * Multiple CRC or Multi-primary tumors； * Epilepsy need treatments(Steroid or anti-epilepsy therapy), * Other malignant tumor history within 5 years, * Over abuse of drugs, medical and psychological or social conditions that might interfere patients or evaluation of the study results, * Any active autoimmune disease or autoimmune disease history (including but not restricted：interstitial pneumonia, uveitis,enteritis, hepatitis,hypophysitis, nephritis, hyperthyroidism, hypothyroidism, asthma need bronchodilators), * Any anti-infection vaccine injection 4 weeks before inclusion , * Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose\>10mg/day prednisolone or equivalent hormone)； * Known or suspicious allergy to any study related drugs, * Any unstable state might cause damage to the safety and compliance of patients, * Pregnant or breast feeding women who has ability to have children while without contraception, * Refuse to sign informed consent