【摘要】 消化道肿瘤免疫治疗仍面临严峻挑战，尤其对于微卫星稳定/错配修复完整等免疫耐药型患者。组蛋白去乙酰化酶抑制剂（HDACi）与免疫检查点抑制剂的联合策略已成为重要突破方向。现有证据表明，HDACi通过表观遗传重编程可有效重塑肿瘤免疫微环境，其机制涵盖抗原呈递增强、免疫抑制解除、T细胞功能激活等多个层面。CAPability-01研究中三联方案取得的突破性疗效（客观缓解率44.0%）充分证实了这一策略的临床价值。然而，联合治疗仍面临毒性管理、生物标志物缺失等关键挑战。未来研究应聚焦于3个核心方向：开发高选择性HDACi以平衡疗效与安全性；建立基于多组学的精准分型体系；优化联合用药的时序和剂量。当前正处于该领域发展的关键阶段，通过基础研究与临床实践的深度协同，HDACi联合免疫治疗有望为消化道肿瘤患者带来新的生存希望，但学术界对其转化前景仍需保持理性预期。更多还原

【Abstract】 Immunotherapy for gastrointestinal tumors continues to face significant challenges, particularly in microsatellite stable/proficient mismatch repair and other immune-resistant subtypes. The combination strategy of histone deacetylase inhibitors(HDACi) with immune checkpoint inhibitors has emerged as a critical breakthrough direction. Accumulating evidence demonstrates that HDACi effectively remodel the tumor immune microenvironment through epigenetic reprogramming, with mechanisms spanning enhanced antigen presentation, immunosuppression alleviation, and T-cell functional activation. The groundbreaking efficacy achieved by the triple regimen in the CAPability-01 trial(objective response rate 44.0%) solidly confirms the clinical value of this approach. Nevertheless, combination therapy still confronts key challenges including toxicity management and the absence of reliable biomarkers. Future research should prioritize three core directions: developing highly selective HDACi to balance efficacy and safety; establishing multi-omics-based precision stratification systems; and optimizing the timing and dosing of combination regimens. The field is currently at a pivotal developmental stage. Through deep integration of basic research and clinical practice, HDACi-immunotherapy combinations hold promise to bring new hope for survival to patients with gastrointestinal cancer, while the academic community should maintain rational expectations regarding its translational potential.更多还原