This study is designed as an open-label, single-arm, single center, phase II clinical trial, aiming to evaluate the efficacy of neoadjuvant Tislelizumab combined with Nab-Paclitaxel for patients with non-metastatic upper tract urothelial carcinoma (UTC). Patients enrolled will receive 2-3 cycles of Tislelizumab in combination with Nab-Paclitaxel every 3 weeks and then undergo radical nephroureterectomy (RNU). The assessment of efficacy is based on the histology of specimen from RNU, and treatment-related adverse events (TRAEs) will be recorded and evaluated according to CTCAE 5.0.

Inclusion Criteria:

1. Males or females aged no less than 18 years old;
2. UTUC indicated by ureteroscopic biopsy and imageological examination (including CT, MRI, or PET-CT), without evidences of metastasis in chest CT scan and abdominal CT scan (T1-4N0-2M0); High risk disease confirmed in accordance with the EAU guidelines.
3. Histologically confirmed urothelial carcinoma or urothelial carcinoma as the major pathological component >50% in the specimen from ureteroscopic biopsy;
4. Suitable and planned to receive RNU.
5. Expected survival time of more than 12 weeks;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2;

6.Agree to provide blood, urine, and tissue samples (for testing PD-L1 expression, HER-2, tumor mutation burden, etc.); 7.The organ function levels must meet the following requirements: Hematological indicators: Absolute neutrophil count ≥1.5×10^9/L, platelet count ≥80×10^9/L, hemoglobin ≥6.0 g/dL (can be maintained through symptomatic treatment); Liver function: Total bilirubin ≤1.5 times the upper limit of normal, alanine transaminase and aspartate transaminase ≤2.5 times the upper limit of normal; Renal function: Baseline ECT renography indicates a total renal glomerular filtration rate (GFR) ≥15 ml/min.

8.Participants are willing to join the study and be able to sign and comply the protocol.

Exclusion Criteria:

1. Concurrent primary malignancies in other sites are excluded, except for those with a history of other malignancies that have been treated and are currently stable.
2. Confirmed bilateral upper tract urothelial carcinoma (UTUC).
3. Presence of urothelial carcinoma in bladder is excluded, except for non-muscle-invasive bladder cancer that can be completely resected via transurethral resection of bladder tumor (TURBT).
4. Received a live attenuated vaccine within 4 weeks before treatment or plan to receive during the study period;
5. Active, known or suspected history of autoimmune disease;
6. Known history of primary immunodeficiency;
7. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
8. Pregnant or breastfeeding female patients;
9. Untreated acute or chronic active Hepatitis B or Hepatitis C infection. Patients receiving antiviral therapy may be eligible if viral load is under monitored, at the discretion of the physician based on the patient's individual condition;
10. Receiving immunosuppressive medication within 4 weeks prior to starting treatment, except nasal, inhaled, topical steroids, or systemic corticosteroids at physiological doses (i.e., not exceeding 10 mg/day of prednisone or equivalent dose of other corticosteroids);
11. Known or suspected allergy to Tislelizumab or Nab-Paclitaxel;
12. Active tuberculosis;
13. Previous treatment with PD-1/PD-L1/CTLA-4 immune checkpoint inhibitors or other immunotherapies;
14. Participation in another clinical study;
15. Fertile men or women without effective contraception;
16. Uncontrolled concurrent illness, including but not limited to:

(1)HIV infection (HIV antibodies positive); (2)Uncontrolled severe infection; (3)Uncontrolled systemic disease (such as severe psychiatric, neurological disorders, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver, or kidney disease, uncontrolled hypertension [i.e., hypertension of CTCAE grade 2 or higher despite treatment]); (4)Active hemorrhage or newly developed thrombotic disease. (5)Renal failure with CKD grade 5 and undergoing dialysis treatment.