{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:02:01Z","timestamp":1784721721283,"version":"3.55.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Application Research of Integrated Traditional Chinese and Western Medicine in Enhanced Recovery After Surgery During the Perioperative Period of Colorectal Cancer","award":["ZDXK202251-2a"],"award-info":[{"award-number":["ZDXK202251-2a"]}]},{"name":"Jiangsu Province 14th Five-Year Medical Key Discipline in Traditional Chinese Surgery","award":["ZDXK202251"],"award-info":[{"award-number":["ZDXK202251"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Colorectal cancer (CRC) recurrence after curative-intent treatment remains a major clinical challenge. Conventional postoperative risk stratification relies on clinicopathological variables, whereas recurrence is increasingly understood as a dynamic biological process shaped by molecular residual disease (MRD), immune editing, tumor microenvironmental remodeling and therapy-resistant cellular states. Circulating tumor DNA (ctDNA) has emerged as a clinically relevant MRD biomarker for identifying patients at high risk of relapse and for refining adjuvant-treatment decisions. At the same time, immune biomarkers such as mismatch repair deficiency, microsatellite instability, tumor mutational burden, antigen-presentation status, T-cell exhaustion, myeloid suppression and spatial immune exclusion determine whether recurrent disease is susceptible to immunotherapy. This Mini Review discusses how MRD and immune escape can be integrated into a biomarker-guided framework for recurrent CRC. We summarize recent evidence supporting ctDNA-guided recurrence surveillance, immune checkpoint blockade in MSI-H\/dMMR CRC, vaccine-based strategies targeting neoantigens or mutant KRAS, and engineered cell therapies including CAR-T, CAR-NK and TCR-engineered approaches. We also discuss how interpretable machine-learning models and SHAP-based feature attribution may help prioritize recurrence biomarkers and enrich clinical trials, provided that models undergo rigorous external validation. A biomarker-guided strategy linking MRD detection, immune profiling and cell-therapy target selection may provide a translational pathway toward more individualized immune intervention for recurrent CRC. In this framework, AI is positioned as an auditable decision-support layer that links ctDNA kinetics, immune biomarker domains, cell-therapy eligibility, and trial-enrichment decisions rather than as an autonomous treatment selector.<\/jats:p>","DOI":"10.3389\/fmed.2026.1906283","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:10:27Z","timestamp":1784718627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting molecular residual disease and immune escape in colorectal cancer recurrence: biomarker-guided immunotherapy and cell therapies"],"prefix":"10.3389","volume":"13","author":[{"given":"Yang","family":"Shan","sequence":"first","affiliation":[{"name":"The First Clinical Medical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lun","family":"Yang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodi","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine","place":["Nanjing, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanwen","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Affiliated Hospital of Nanjing 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