Optimizing Immunotherapy Combined With Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Inclusion Criteria: 1. Age 18-75 years, regardless of gender; 2. Pathologically confirmed rectal adenocarcinoma with immunohistochemical results indicating pMMR (proficient mismatch repair) or genetic testing confirming MSS (microsatellite stability); 3. Staged as clinical stage II/III (cT3-T4N0 or cT2-4N+, no distant metastasis, per the 8th Edition AJCC Cancer Staging Manual, 2018) via MRI or endoscopic ultrasound, and meeting any one of the following: * cT3 with tumor inferior margin ≤ 6 cm from the anal verge; * cT3c/d with tumor inferior margin ≥ 6-12 cm from the anal verge; ③ cN2; ④ cT4; ⑤ MRF+ (mesorectal fascia involvement); ⑥ EMVI+ (extramural vascular invasion); 4. ECOG performance status 0-1; 5. Meeting basic laboratory criteria (e.g., hematologic, hepatic, and renal function); 6. No history of hypersensitivity to 5-Fu-based agents or platinum-based drugs; 7. Patients with primary rectal cancer must have received no prior surgery (excluding palliative colostomy), chemotherapy, or other antitumor therapies from diagnosis to enrollment; 8. No prior radiation to the planned radiotherapy site; 9. Signed informed consent form. Exclusion Criteria: 1. Prior treatment with anti-PD-1/L1 and/or anti-CTLA-4 immunotherapy or other investigational immunotherapeutic agents; 2. History of severe autoimmune diseases, including active inflammatory bowel disease (IBD) (e.g., Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g., granulomatosis with polyangiitis); 3. Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis; 4. Risk factors for bowel perforation, such as active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis, or other known predisposing conditions; 5. History of other malignancies, except for cured non-melanoma skin cancer or cervical carcinoma in situ; 6. Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or uncontrolled arrhythmia; 7. Physical examination findings or clinical laboratory abnormalities deemed by the investigator to interfere with study outcomes or increase treatment-related risks, or other uncontrolled comorbidities; 8. Pregnant or breastfeeding women; 9. Congenital or acquired immunodeficiency disorders, including HIV infection, or history of organ/stem cell transplantation; 10. Active hepatitis B (HBV-DNA ≥2000 U/mL), hepatitis C (HCV), or active tuberculosis infection; 11. Prior administration of cancer vaccines or receipt of any vaccine within 4 weeks before treatment initiation (Note: Seasonal inactivated influenza vaccines are permitted; live-attenuated intranasal vaccines are prohibited); 12. Concurrent use of immunomodulators, chemotherapy, investigational drugs, or long-term corticosteroids (≥10 mg/day prednisone equivalent); 13. Patients with psychiatric disorders, substance abuse, or social circumstances that may compromise compliance, as assessed by the investigator; 14. Hypersensitivity or contraindications to the study medications.