The purpose of this study is to explore the efficacy and safety of involved-field radiotherapy-TNT combined with PD-1 inhibitors in pMMR locally advanced rectal cancer.

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
3. Pathologic diagnosis of adenocarcinoma of the rectum, definite pMMR type;
4. Clinical staging of T3-4NanyM0 or T1-2N+M0 (based on AJCC 8th edition staging criteria);
5. The lower margin of the primary tumor is located below the peritoneal reflex or the lower margin of the tumor is ≤10 cm from the anal verge;
6. Pre-enrollment laboratory indicators meet the following indicator ranges： 1)Blood: absolute neutrophils ≥1.5×10^9/L, platelets ≥100×10^9/L, hemoglobin ≥90g/L; 2)Liver and kidney function: ALT/AST ≤ 2.5 x ULN, total bilirubin ≤ 1.5 x ULN, creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 60mL/min (Cockcroft-Gault formula)； 3)Coagulation: INR ≤ 1.5, APTT ≤ 1.5 x ULN (for those not receiving anticoagulation)；
7. Women or men of childbearing potential need to agree to use effective contraception during the study and for 6 months after the last treatment session;
8. Voluntary written informed consent and commitment to complete the full treatment and follow-up program.

Exclusion Criteria:

1. Pathologic type is other specific types such as neuroendocrine carcinoma, squamous carcinoma, etc;
2. Previous radiotherapy, chemotherapy, targeted or immunotherapy for rectal cancer;
3. Active autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis requiring long-term immunosuppressive therapy)；
4. Presence of active infection (e.g. HIV, HBV/HCV viral load positive requiring stabilization on antiretroviral therapy)；
5. Severe cardiovascular disease (e.g., myocardial infarction within 6 months, unstable angina, uncontrolled hypertension >160/100 mmHg)；
6. History of other malignant tumors (except non-melanoma skin cancers, cervical cancer in situ, etc. cured for ≥5 years)；
7. Uncontrolled diabetes mellitus (HbA1c > 8%), abnormal thyroid function (TSH outside normal range and requiring pharmacologic intervention)；
8. Severe chronic bowel disease (e.g., Crohn's disease, active ulcerative colitis)； Patients deemed by the investigator to be unsuitable for participation in this study.