He Yang, Gu Wendong, Shao Yingjie
Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Front Immunol. 2025 Aug 8;16:1631620. doi: 10.3389/fimmu.2025.1631620. eCollection 2025.
Locally advanced rectal cancer (LARC) constitutes a particularly challenging subtype of rectal cancer. Although traditional neoadjuvant chemoradiotherapy (nCRT) has demonstrated efficacy in enhancing local disease control and promoting sphincter preservation, its impact on long-term survival outcomes remains suboptimal. In recent years, combinatorial approaches integrating immune checkpoint inhibitors (ICIs) with nCRT have garnered increasing research interest. Nevertheless, individuals with proficient mismatch repair (pMMR)/microsatellite stable (MSS) LARC exhibit a notable resistance to immunotherapeutic strategies. This review thoroughly assesses the molecular features and treatment challenges linked to pMMR/MSS LARC, elucidates the functional pathways of ICIs, and explores their prospective synergistic effects when administered alongside nCRT. Moreover, recent progress in clinical investigations is summarized, and the utility of emerging biomarkers in facilitating patient selection and assessing treatment efficacy is critically appraised.
局部晚期直肠癌（LARC）是直肠癌中一种特别具有挑战性的亚型。尽管传统的新辅助放化疗（nCRT）已证明在增强局部疾病控制和促进括约肌保留方面有效，但其对长期生存结果的影响仍不尽人意。近年来，将免疫检查点抑制剂（ICIs）与nCRT相结合的联合方法已引起越来越多的研究兴趣。然而，错配修复功能正常（pMMR）/微卫星稳定（MSS）的LARC患者对免疫治疗策略表现出显著抗性。本综述全面评估了与pMMR/MSS LARC相关的分子特征和治疗挑战，阐明了ICIs的功能途径，并探讨了其与nCRT联合使用时的潜在协同效应。此外，总结了临床研究的最新进展，并对新兴生物标志物在促进患者选择和评估治疗疗效方面的效用进行了批判性评估。
