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Abstract Tislelizumab is a humanized IgG4 monoclonal antibody targeting programmed death-1 (PD-1), uniquely engineered to minimize Fcγ-receptor (FcγR) binding on macrophages, thereby reducing macrophage-mediated clearance of PD-1-expressing effector T cells. This design sustains antitumor immune responses and distinguishes it mechanistically from earlier PD-1 inhibitors. Clinical evidence from the phase III RATIONALE trials demonstrates broad efficacy across multiple solid tumors, including esophageal squamous cell carcinoma (ESCC), gastric and gastroesophageal junction (G/GEJ) adenocarcinoma, hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC). In ESCC, tislelizumab significantly improved overall survival in both second-line (RATIONALE-302) and first-line (RATIONALE-306) settings, while in G/GEJ adenocarcinoma (RATIONALE-305), dual primary endpoints of overall survival were achieved in both PD-L1-positive and intention-to-treat populations. The RATIONALE-301 trial in HCC showed noninferiority to sorafenib with improved tolerability. In NSCLC (RATIONALE-304 and 307), combination therapy with platinum-based chemotherapy prolonged progression-free survival and response rates, while RATIONALE-312 extended benefits to extensive-stage SCLC with survival improvement and manageable toxicity. Across studies, adverse events were consistent with the PD-1 inhibitor class and generally less frequent or severe than chemotherapy backbones. Collectively, tislelizumab delivers broad antitumor activity, durable responses, and a favorable safety profile. Ongoing investigations are exploring its role in perioperative, combinatorial, and biomarker-driven strategies, supporting its emergence as a versatile PD-1 inhibitor with potential to reshape contemporary oncology practice.