REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1631620
Research Progress on Immunotherapy Combined with Neoadjuvant Concurrent Chemoradiotherapy in pMMR/MSS Locally Advanced Rectal Cancer
Provisionally accepted
- Department of Hepatobiliary Surgery, Third Affiliated Hospital of Soochow University, Changzhou, China
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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.
Keywords: combination therapy, immune checkpoint inhibitors, Locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, MSS
Received: 20 May 2025; Accepted: 25 Jul 2025.
Copyright: © 2025 He, Gu and Shao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yingjie Shao, Department of Hepatobiliary Surgery, Third Affiliated Hospital of Soochow University, Changzhou, China
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