This study aims to elucidate the effects of neoadjuvant Tislelizumab combined with chemotherapy in locally advanced Microsatellite Stable (MSS) colon cancer.

The standard treatment for locally advanced colon cancer is complete mesocolic excision (CME) followed by adjuvant chemotherapy. The MOSAIC and 16968 studies have shown that about 30% of patients experience recurrence and metastasis within 6-7 years after surgery. Neoadjuvant chemotherapy may improve the prognosis of colon cancer patients. The significant tumor remission after neoadjuvant therapy probably indicates a better long-term survival for patients. The OPTICAL and Fluoropyrimidine Oxaliplatin and Targeted Receptor Pre-Operative Therapy (FoxTROT) studies have shown that approximately 35% of patients are resistant to oxaliplatin-containing neoadjuvant chemotherapy, with a pathological complete response (pCR) rate of less than 10% and uncertain survival improvement. Moreover, previous study shown that immunotherapy has unsatisfied efficacy for microsatellite stable (MSS) colon cancer. Therefore, it is necessary to explore more effective neoadjuvant treatment strategy for tumor therapy.

Immunogenic cell death will be enhanced by oxaliplatin-induced immunogenicity and combined with anti-programmed cell death 1 (PD-1) monoclonal antibodies for neoadjuvant therapy. The study will conduct 2 or 4 cycles of Tislelizumab with Oxaliplatin and Capecitabine, followed by CME surgery. The study's primary endpoint is the proportion of pCR in the pathological specimens of surgically resected tumors.

Inclusion Criteria:

• Age ≥18 years old and ≤75 years old.
• Pathologically diagnosed MSS ((confirmed by microsatellite stable detection or next-generation target sequencing) or (confirmed by immunohistochemistry)) colon adenocarcinoma.
• The lower edge of the tumor is more than 12cm from the anus as measured by colonoscopy and the lower edge of the tumor cannot be directly palpated during rectal examination.
• Enhanced CT stage T4 or T1-4 N+ without multiple primary tumors or distant metastasis.
• The Eastern Cooperative Oncology Group physical status score is 0-1.
• Life expectancy is expected to be more than 1 year.
• First diagnosis, no previous anti-tumor treatment received, and no chemotherapy contraindications.
• Appropriate organ function is defined as follows: Hemoglobin level ≥ 60g/L, Neutrophil count ≥ 1.5×10^9/L, Platelet count ≥ 75×10^9/L, Serum total bilirubin ≤ 1.5× the upper limit of normal (UNL), Aspartate aminotransferase (AST) ≤ 2× UNL, Alanine aminotransferase (ALT) ≤ 3× UNL, Serum creatinine ≤ 1.5× UNL.
• Informed consent, able to understand the study protocol and willing to participate in the study, and will provide written informed consent.

Exclusion Criteria:

• Enhanced CT stage (T1-3N0M0)
• Multifocal colorectal cancer.
• CT or MRI in the mid-sagittal plane shows that the lower border of the tumor is below the line connecting the sacrococcygeal promontory and the upper border of the pubic symphysis.
• Tumor obstruction or high risk of obstruction, bleeding, and/or perforation requiring emergency surgery or stent placement.
• Cannot tolerate chemotherapy or immunotherapy, such as but not limited to bone marrow suppression.
• History of malignant tumors, except for basal cell carcinoma, papillary thyroid carcinoma, and various in situ cancers.
• Acute exacerbation of important organ diseases (such as but not limited to chronic obstructive pulmonary disease, coronary heart disease, and renal insufficiency) and/or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia, and myocarditis), American Society of Anesthesiologists score > 3 points.
• Mental disorders, illiteracy, or language communication barriers that prevent the understanding of the study protocol.
• Peripheral sensory neuropathy, unable to receive oxaliplatin-based chemotherapy.
• Continuous use of glucocorticoids for more than 3 days within 1 month prior to signing the informed consent form, or having comorbidities requiring the use of glucocorticoid therapy.
• Unable to undergo enhanced CT examination
• Pregnancy or lactation.
• Refused to participate in this study.
• Other situations in which the researcher deems unsuitable for this study.