{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:53:26Z","timestamp":1790949206208,"version":"4.1.0"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1631620","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:28:21Z","timestamp":1754630901000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Research progress on immunotherapy combined with neoadjuvant concurrent chemoradiotherapy in pMMR\/MSS locally advanced rectal cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Yang","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendong","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3322\/caac.21871","article-title":"Cancer statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.15438","article-title":"A review of neoadjuvant chemoradiotherapy for locally advanced rectal cancer","volume":"12","author":"Li","year":"2016","journal-title":"Int J Biol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.30805","article-title":"What has preoperative radio(chemo)therapy brought to localized rectal cancer patients in terms of perioperative and long-term outcomes over the past decades? A systematic review and meta-analysis based on 41,121 patients","volume":"141","author":"Ma","year":"2017","journal-title":"Int J Cancer."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2210175","article-title":"Prevalence of mismatch-repair deficiency in rectal adenocarcinomas","volume":"387","author":"Papke","year":"2022","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042020-042741","article-title":"Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance","volume":"16","author":"Bagchi","year":"2021","journal-title":"Annu Rev Pathol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"101480","DOI":"10.1016\/j.smim.2021.101480","article-title":"Emerging concepts in PD-1 checkpoint biology","volume":"52","author":"Pauken","year":"2021","journal-title":"Semin Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1016\/j.celrep.2018.06.054","article-title":"Antigen-presenting cell-intrinsic PD-1 neutralizes PD-L1 in cis to attenuate PD-1 signaling in T cells","volume":"24","author":"Zhao","year":"2018","journal-title":"Cell Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1571892","article-title":"PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations","volume":"15","author":"Jiang","year":"2019","journal-title":"Hum Vaccin Immunother."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.2736","article-title":"Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresecta ble or metastatic melanoma","volume":"33","author":"SChadendorf","year":"2015","journal-title":"J Clin Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","article-title":"Approaches to treat immune hot, altered and cold tumours with combination immunotherapies","volume":"18","author":"Galon","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v16.i3.643","article-title":"Prognostic and predictive role of immune microenvironment in colorectal cancer","volume":"16","author":"Kuznetsova","year":"2024","journal-title":"World J Gastrointest Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s11864-021-00870-z","article-title":"Beyond microsatellite instability: evolving strategies integrating immunotherapy for microsatellite sta ble colorectal cancer","volume":"22","author":"Pecci","year":"2021","journal-title":"Curr Treat Options Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2201445","article-title":"PD-1 blockade in mismatch repair-deficient, locally advanced rectal cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02030","article-title":"Evaluation of CD3 and CD8 T-cell immunohistochemistry for prognostication and prediction of benefit from adjuvant chemotherapy in early-stage colorectal cancer within the QUASAR trial","volume":"42","author":"Williams","year":"2024","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"101949","DOI":"10.1016\/j.ctrv.2019.101949","article-title":"The local inflammatory response in colorectal cancer - Type, location or density? A systematic review and meta-analysis","volume":"83","author":"Alexander","year":"2020","journal-title":"Cancer Treat Rev"},{"key":"B17","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/s41421-023-00605-4","article-title":"Single cell dynamics of tumor specificity vs bystander activity in CD8(+) T cells define the diverse immune landscapes in colorectal cancer","volume":"9","author":"Borr\u00e0s","year":"2023","journal-title":"Cell Discov"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.0910","article-title":"Effect of combined immune checkpoint inhibition vs best supportive care alone in patients with advanced colorectal cancer: the canadian cancer trials group CO","volume":"6","author":"Chen","year":"2020","journal-title":"26 Study. JAMA Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02736","article-title":"Lenvatinib plus pembrolizumab versus standard of care for previously treated metastatic colorectal cancer: final analysis of the randomized, open-label, phase III LEAP-017 study","volume":"42","author":"Kawazoe","year":"2024","journal-title":"J Clin Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30027-0","article-title":"Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial","volume":"20","author":"Eng","year":"2019","journal-title":"Lancet Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01654","article-title":"Cytotoxic chemotherapy as an immune stimulus: A molecular perspective on turning up the immunological heat on cancer","volume":"10","author":"Opzoomer","year":"2019","journal-title":"Front Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1433981","article-title":"PD-1\/PD-L1 pathway: an adaptive immune resistance mechanism to immunogenic chemotherapy in colorectal cancer","volume":"7","author":"Dosset","year":"2018","journal-title":"Oncoimmunology."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3690","article-title":"5-Fluorouracil selectively kills tumor-associated myeloid-derived suppressor cells resulting in enhanced T cell-dependent antitumor immunity","volume":"70","author":"Vincent","year":"2010","journal-title":"Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(22)00274-1","article-title":"Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): a multicentre, open-label, randomised, controlled, phase 2 trial","volume":"23","author":"Antoniotti","year":"2022","journal-title":"Lancet Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02728","article-title":"Upfront fluorouracil, leucovorin, oxaliplatin, and irinotecan plus bevacizumab with or without atezolizumab for patients with metastatic colorectal cancer: updated and overall survival results of the ATEZOTRIBE study","volume":"42","author":"Antoniotti","year":"2024","journal-title":"J Clin Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI127458","article-title":"Type I IFN protects cancer cells from CD8+ T cell-mediated cytotoxicity after radiation","volume":"129","author":"Chen","year":"2019","journal-title":"J Clin Invest."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1523097","article-title":"Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells","volume":"8","author":"Krombach","year":"2019","journal-title":"Oncoimmunology."},{"key":"B28","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.canlet.2019.02.048","article-title":"Mechanisms and therapeutic potentials of cancer immunotherapy in combination with radiotherapy and\/or chemotherapy","volume":"452","author":"Yu","year":"2019","journal-title":"Cancer Lett"},{"key":"B29","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/s41392-022-01102-y","article-title":"Radiotherapy combined with immunotherapy: the dawn of cancer treatment","volume":"7","author":"Zhang","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx790","article-title":"Radiotherapy and anti-PD-1\/PD-L1 combinations in lung cancer: building better translational research platforms","volume":"29","author":"Kordbacheh","year":"2018","journal-title":"Ann Oncol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.07.009","article-title":"Phase 1 study of chemoradiotherapy combined with nivolumab \u00b1 Ipilimumab for the curative treatment of muscle-invasive bladder cancer","volume":"82","author":"de Ruiter","year":"2022","journal-title":"Eur Urol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3213","article-title":"Preoperative Chemoradiotherapy plus Nivolumab before Surgery in Patients with Microsatellite Sta ble and Microsatellite Instability-High Locally Advanced Rectal Cancer","volume":"28","author":"Bando","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-024-02730-7","article-title":"Three-year outcomes of preoperative chemoradiotherapy plus nivolumab in microsatellite sta ble and microsatellite instability-high locally advanced rectal cancer","volume":"131","author":"Tsukada","year":"2024","journal-title":"Br J Cancer."},{"key":"B34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1200\/JCO.2022.40.4_suppl.099","article-title":"Phase II study of durvalumab following neoadjuvant chemoRT in operable rectal cancer: NSABP FR-2","volume":"40","author":"George","year":"2022","journal-title":"J Clin Oncol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"101824","DOI":"10.1016\/j.esmoop.2023.101824","article-title":"Phase II study of capecitabine-based concomitant chemoradiation followed by durvalumab as a neoadjuvant strategy in locally advanced rectal cancer: the PANDORA trial","volume":"8","author":"Grassi","year":"2023","journal-title":"ESMO Open"},{"key":"B36","doi-asserted-by":"publisher","first-page":"S432","DOI":"10.1016\/j.annonc.2023.09.1790","article-title":"599P R-IMMUNE: A phase Ib\/II study to evaluate safety and efficacy of atezolizumab combined with radio-chemotherapy in a preoperative setting for patients with locally advanced rectal cancer (LARC)","volume":"34","author":"Carrasco","year":"2023","journal-title":"Ann Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"S537","DOI":"10.1016\/j.annonc.2021.08.919","article-title":"397P R-IMMUNE interim analysis: A phase Ib\/II study to evaluate safety and efficacy of atezolizumab combined with radio-chemotherapy in a preoperative setting for patients with localized rectal cancer","volume":"32","author":"Carrasco","year":"2021","journal-title":"Ann Oncol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1057947","article-title":"Interim result of phase II, prospective, single-arm trial of long-course chemoradiotherapy combined with concurrent tislelizumab in locally advanced rectal cancer","volume":"13","author":"Gao","year":"2023","journal-title":"Front Oncol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41392-024-01762-y","article-title":"Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study","volume":"9","author":"Yang","year":"2024","journal-title":"Signal Transduction Targeted Ther"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03360-5","article-title":"Neoadjuvant chemoradiation with or without PD-1 blockade in locally advanced rectal cancer: a randomized phase 2 trial","volume":"31","author":"Yang","year":"2025","journal-title":"Nat Med"},{"key":"B41","doi-asserted-by":"publisher","first-page":"S464","DOI":"10.1016\/j.annonc.2024.08.639","article-title":"570P A phase II clinical study of fruquintinib (Fru) combined with toripalimab (Tor) and short-course radiotherapy (SCRT) as neoadjuvant therapy for locally advanced rectal cancer (LARC)","volume":"35","author":"Chen","year":"2024","journal-title":"Ann Oncol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003554","article-title":"single-arm trial of preoperative short-course radiotherapy followed by chemotherapy and camrelizumab in locally advanced rectal cancer","volume":"9","author":"Lin","year":"2021","journal-title":"J Immunother Cancer"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.06.015","article-title":"Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial","volume":"35","author":"Lin","year":"2024","journal-title":"Ann Oncol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1470-2045(20)30555-6","article-title":"Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial","volume":"22","author":"Bahadoer","year":"2021","journal-title":"Lancet Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz186","article-title":"Long-course preoperative chemoradiation versus 5 \u00d7 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study","volume":"30","author":"Cise\u0142","year":"2019","journal-title":"Ann Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01667","article-title":"Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR)","volume":"40","author":"Jin","year":"2022","journal-title":"J Clin Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/codi.17090","article-title":"Preoperative short-course radiotherapy followed by chemotherapy and PD-1 inhibitor administration for locally advanced rectal cancer: A study protocol of a randomized phase II\/III trial (STELLAR II study)","volume":"26","author":"Zhang","year":"2024","journal-title":"Colorectal Disease."},{"key":"B48","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1186\/s12885-024-12254-1","article-title":"The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study","volume":"24","author":"Xu","year":"2024","journal-title":"BMC Cancer"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.101955","article-title":"A retrospective cohort study of neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitors in locally advanced rectal cancer","volume":"44","author":"Chen","year":"2024","journal-title":"Trans Oncol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71199-4","article-title":"Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data","volume":"16","author":"Breugom","year":"2015","journal-title":"Lancet Oncol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003471","article-title":"Total neoadjuvant therapy in rectal cancer: A systematic review and meta-analysis of treatment outcomes","volume":"271","author":"Petrelli","year":"2020","journal-title":"Ann Surg"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/bjs\/znad177","article-title":"Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials","volume":"110","author":"Donnelly","year":"2023","journal-title":"Br J Surg"},{"key":"B53","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1186\/s13014-020-01673-6","article-title":"Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma","volume":"15","author":"Shamseddine","year":"2020","journal-title":"Radiat Oncol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"115428","DOI":"10.1016\/j.ejca.2025.115428","article-title":"Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced microsatellite sta ble rectal adenocarcinoma: The Averectal study","volume":"222","author":"Shamseddine","year":"2025","journal-title":"Eur J Cancer."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.1683","article-title":"Use of total neoadjuvant therapy for locally advanced rectal cancer: initial results from the pembrolizumab arm of a phase 2 randomized clinical trial","volume":"7","author":"Rahma","year":"2021","journal-title":"JAMA Oncol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"3609","DOI":"10.1200\/JCO.2022.40.16_suppl.3609","article-title":"PKUCH 04 trial: Total neoadjuvant chemoradiation combined with neoadjuvant PD-1 blockade for pMMR\/MSS locally advanced middle to low rectal cancer","volume":"40","author":"Wu","year":"2022","journal-title":"J Clin Oncol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.16_suppl.e15602","article-title":"Preliminary efficacy and safety of total neoadjuvant therapy combined with PD-L1 blockade in pMMR\/MSS locally advanced rectal cancer (ESTIMATE): A prospective, single-arm, phase II trial","volume":"42","author":"Zhang","year":"2024","journal-title":"J Clin Oncol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.02261","article-title":"Randomized phase II trial of immunotherapy-based total neoadjuvant therapy for proficient mismatch repair or microsatellite sta ble locally advanced rectal cancer (TORCH)","volume":"42","author":"Xia","year":"2024","journal-title":"J Clin Oncol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-20-3054","article-title":"Tumor mutational burden as a predictor of immunotherapy response: is more always better","volume":"27","author":"Strickler","year":"2021","journal-title":"Clin Cancer Res"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30445-9","article-title":"Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study","volume":"21","author":"Marabelle","year":"2020","journal-title":"Lancet Oncol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.21037\/jgo.2018.05.06","article-title":"Beyond microsatellite testing: assessment of tumor mutational burden identifies subsets of colorectal cancer who may respond to immune checkpoint inhibition","volume":"9","author":"Fabrizio","year":"2018","journal-title":"J Gastrointest Oncol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s11523-020-00703-3","article-title":"Tumor mutation burden as a potential biomarker for PD-1\/PD-L1 inhibition in advanced non-small cell lung cancer","volume":"15","author":"Huang","year":"2020","journal-title":"Target Oncol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2024.03.007","article-title":"Tumor mutational burden for the prediction of PD-(L)1 blockade efficacy in cancer: challenges and opportunities","volume":"35","author":"Wang","year":"2024","journal-title":"Ann Oncol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0805-8","article-title":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","volume":"26","author":"Chalabi","year":"2020","journal-title":"Nat Med"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S91025","article-title":"The expression status and prognostic significance of programmed cell death 1 ligand 1 in gastrointestinal tract cancer: a systematic review and meta-analysis","volume":"8","author":"Huang","year":"2015","journal-title":"Onco Targets Ther"},{"key":"B66","doi-asserted-by":"publisher","first-page":"636","DOI":"10.3390\/cancers14030636","article-title":"Tumor-infiltrating lymphocytes as biomarkers of treatment response and long-term survival in patients with rectal cancer: A systematic review and meta-analysis","volume":"14","author":"Orhan","year":"2022","journal-title":"Cancers (Basel)."},{"key":"B67","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/1748-717X-6-49","article-title":"Density of CD4(+) and CD8(+) T lymphocytes in biopsy samples can be a predictor of pathological response to chemoradiotherapy (CRT) for rectal cancer","volume":"6","author":"Yasuda","year":"2011","journal-title":"Radiat Oncol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"5767","DOI":"10.3390\/ijms24065767","article-title":"The gut microbiome, microsatellite status and the response to immunotherapy in colorectal cancer","volume":"24","author":"Sillo","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.08.010","article-title":"Fusobacterium nucleatum, a key pathogenic factor and microbial biomarker for colorectal cancer","volume":"31","author":"Wang","year":"2023","journal-title":"Trends Microbiol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i32.5362","article-title":"Faecal microbiota transplantation enhances efficacy of immune checkpoint inhibitors therapy against cancer","volume":"27","author":"Kang","year":"2021","journal-title":"World J Gastroenterol"},{"key":"B71","doi-asserted-by":"publisher","first-page":"102315","DOI":"10.1016\/j.eclinm.2023.102315","article-title":"Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite st able metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)","volume":"66","author":"Zhao","year":"2023","journal-title":"EClinicalMedicine."},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30789-X","article-title":"International validation of the consensus Immunoscore for the classification of colon cancer: a prognostic and accuracy study","volume":"391","author":"Pag\u00e8s","year":"2018","journal-title":"Lancet."},{"key":"B73","doi-asserted-by":"publisher","first-page":"S449","DOI":"10.1016\/j.annonc.2020.08.602","article-title":"491P Neoadjuvant nivolumab in early stage colorectal cancer","volume":"31","author":"Avallone","year":"2020","journal-title":"Ann Oncol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02615","article-title":"Using circulating tumor DNA in colorectal cancer: current and evolving practices","volume":"40","author":"Malla","year":"2022","journal-title":"J Clin Oncol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00470","article-title":"Serial monitoring\u00a0of\u00a0circulating tumor DNA in patients with metastatic colorectal cancer to predict the therapeutic response","volume":"10","author":"Jia","year":"2019","journal-title":"Front Genet"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-3155","article-title":"Early evaluation of circulating tumor DNA as marker of therapeutic efficacy in metastatic colorectal cancer patients (PLACOL study)","volume":"23","author":"Garlan","year":"2017","journal-title":"Clin Cancer Res"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02791-w","article-title":"Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer","volume":"30","author":"Shitara","year":"2024","journal-title":"Nat Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01553-w","article-title":"Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial","volume":"27","author":"Nakamura","year":"2021","journal-title":"Nat Med"},{"key":"B79","doi-asserted-by":"publisher","first-page":"103945","DOI":"10.1016\/j.ebiom.2022.103945","article-title":"Response prediction and risk stratification of patients with rectal cancer after neoadjuvant therapy through an analysis of circulating tumour DNA","volume":"78","author":"Liu","year":"2022","journal-title":"EBioMedicine."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-315852","article-title":"Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study","volume":"68","author":"Tie","year":"2019","journal-title":"Gut."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-19-1996","article-title":"MRI tumor regression grade and circulating tumor DNA as complementary tools to assess response and guide therapy adaptation in rectal cancer","volume":"26","author":"Khakoo","year":"2020","journal-title":"Clin Cancer Res"},{"key":"B82","doi-asserted-by":"publisher","first-page":"105548","DOI":"10.1016\/j.ebiom.2024.105548","article-title":"Circulating tumour DNA in predicting and monitoring survival of patients with locally advanced rectal cancer undergoing multimodal treatment: long-term results from a prospective multicenter study","volume":"112","author":"Zhou","year":"2025","journal-title":"EBioMedicine."},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00146-2","article-title":"Clinical application of circulating tumour DNA in colorectal cancer","volume":"8","author":"Loft","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-20-1248","article-title":"Therapeutic targeting of checkpoint receptors within the DNAM1 axis","volume":"11","author":"Alteber","year":"2021","journal-title":"Cancer Discov"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05593-1","article-title":"\u03b3\u03b4 T cells are effectors of immunotherapy in cancers with HLA class I defects","volume":"613","author":"de Vries","year":"2023","journal-title":"Nature."},{"key":"B86","doi-asserted-by":"publisher","first-page":"e504","DOI":"10.1002\/mgg3.504","article-title":"A comprehensive study of\u00a0immunology repertoires in both preoperative stage and postoperative stage in patients with colorectal cancer","volume":"7","author":"Liu","year":"2019","journal-title":"Mol Genet Genomic Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13045-022-01273-9","article-title":"Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies","volume":"15","author":"Lu","year":"2022","journal-title":"J Hematol Oncol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.canlet.2020.12.045","article-title":"Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity","volume":"502","author":"Donlon","year":"2021","journal-title":"Cancer Lett"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-019-03094-9","article-title":"Separating or combining immune checkpoint inhibitors (ICIs) and radiotherapy in the treatment of NSCLC brain metastases","volume":"146","author":"Li","year":"2020","journal-title":"J Cancer Res Clin Oncol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1631620\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T05:28:21Z","timestamp":1754630901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1631620\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,8]]},"references-count":89,"alternative-id":["10.3389\/fimmu.2025.1631620"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1631620","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,8]]},"article-number":"1631620"}}