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Neoadjuvant tislelizumab plus gemcitabine and nab-paclitaxel is promising for improving the resection rate in BRPC, with a favorable safety profile, and NT5DC2, FAM3D, CXCL5, and TMT1B may serve as candidate biomarkers of preoperative drug resistance, and tumor immune microenvironment analysis further reveals immune microenvironment remodeling in postoperative tumors from treatment-sensitive patients.