Neoadjuvant Short-Course Radiotherapy Followed by CAPOX Plus PD-1 Antibody and IL-2 in Locally Advanced Rectal Cancer (PRIDE01)

Inclusion Criteria:

* Age 18 to 70 years at enrollment.
* Histologically confirmed rectal adenocarcinoma with the inferior tumor border within 12 cm of the anal verge.
* Pelvic MRI stage T3-T4, or any T stage with regional lymph-node involvement.
* Absolute neutrophil count \>=1.5 x 10\^9/L and platelet count \>=75 x 10\^9/L.
* Total bilirubin \<=1.5 x the upper limit of normal; aspartate aminotransferase and alanine aminotransferase \<=2.5 x the upper limit of normal.
* Serum creatinine \<=1.5 x the upper limit of normal.
* Eastern Cooperative Oncology Group performance status 0 or 1.
* Ability and willingness to provide written informed consent.

Exclusion Criteria:

* Distant metastatic disease.
* Recurrent rectal cancer.
* Tumor-related bleeding or perforation, or another condition requiring emergency surgery.
* Previous systemic anticancer treatment for rectal cancer.
* A concurrent malignancy other than colorectal cancer.
* Active autoimmune disease, or a history of autoimmune disease requiring systemic corticosteroids or other immunosuppressive therapy.
* Interstitial lung disease, non-infectious pneumonitis, or another uncontrolled systemic disease.
* Unresolved toxicity of grade 2 or higher from previous treatment, except anemia, alopecia or pigmentation changes.
* Previous treatment targeting PD-1, PD-L1 or CTLA-4.
* Pregnancy or breastfeeding.
* Human immunodeficiency virus infection or acquired immunodeficiency syndrome.
* Known hypersensitivity to any protocol treatment component.