Total Neoadjuvant Treatment With or Without Tislelizumab for Locally Advanced Rectal Cancer.

Inclusion Criteria: * Subjects with histologically confirmed primary (non-recurrent) LARC (tumor 12 cm or less from the anal verge, as assessed by rigid proctoscopy), stage T3-4 N0 or TX N+ according to base-line pelvic MRI and PET-CT. * Patients who are planned for TNT and are surgical candidates as determined by the treating physician. * No prior chemotherapy, immunotherapy, radiotherapy or surgery for rectal cancer. * No prior radiotherapy to the pelvis, for any reason. * Able to provide the FFPE block or 10 unstained slides from the colonoscopy for confirmation of the diagnosis, CPS status and for investigational purposes. * Age 18 years or more. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) \< 2. * Screening laboratory values must meet the following criteria (using CTCAEv5.0): i) WBC \> 2000/µL ii) Neutrophils \> 1500/ µL iii) Platelets \> 100 x 103/ µL iv) Hemoglobin \> 9.0 g/dL v) Serum creatinine \< 1.5 x ULN or calculated creatinine clearance \> 60 mL/min (using the Cockcroft Gault formula) vi) AST and ALT \< 2.5 x ULN. vii) Total bilirubin \< 1.5 x ULN (total bilirubin must be \< 3 x ULN for patients with Gilberts syndrome). * Ability to swallow tablets. * Adequate contraception in fertile patients; using a highly effective method of birth control for the duration of the study, and for at least 9 months after the last dose of chemotherapy and 120 days after the last dose of immunotherapy. * Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 7 days prior to the start of treatment. * Women must not be breastfeeding. * Signed written IRB approved informed consent. This must be obtained before the performance of any protocol related procedure that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatments, and laboratory testing. Exclusion Criteria: * Active or background history of an autoimmune disease except for type I diabetes mellitus, hypothyroidism requiring hormone replacement only and skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment. * Medical history of vasculitis. * Prior organ transplant, including allogenic bone marrow transplantation. * Grade \> 1 peripheral sensory neuropathy. * Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co- stimulation or checkpoint pathways. * Any prior active malignancy \< 2 years before trial entry except for any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast). * Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy. * Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). * Known acute hepatitis B, known chronic hepatitis B infection with active untreated disease, or known active hepatitis C infection. In participants with a history of HBV or HCV, participants with detectable viral loads will be excluded.