{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:39:51Z","timestamp":1792708791138,"version":"4.5.0"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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>Concurrent chemoradiotherapy (CRT) is the backbone of curative treatment for locally advanced cervical cancer, and PD-(L)1 blockade has entered first-line practice. Yet the pivotal trials diverge: pembrolizumab added to CRT improved survival in KEYNOTE-A18, whereas durvalumab did not in CALLA. Most prior syntheses organize the cervical tumor immune microenvironment by cell type and rely on cross-sectional, pre-treatment sampling, and several predate KEYNOTE-A18 and recent longitudinal multi-omic data. Here we reframe the question along the treatment time axis. Section 1.1 reports that evidence base in full, under tiered eligibility criteria. Drawing on the still-small body of studies with paired or serial pre-, on-, and post-treatment sampling of tumor and blood, we reconstruct four sequential states: an HPV-shaped baseline ecology; an early immunogenic priming window driven by DNA-damage sensing and type I interferon; a mid-treatment window in which intratumoral activation coexists with radiation-induced lymphodepletion and compensatory checkpoint upregulation; and a post-treatment state of viral-antigen persistence, minimal residual disease, and adaptive resistance. We use this lens to interpret CRT\u2013immune checkpoint inhibitor (ICI) trial heterogeneity without over-attributing it, and derive a falsifiable prediction, which neither pivotal trial can adjudicate and which the best available randomized-evidence synthesis currently opposes: blockade delivered within the priming window may outperform equal exposure given as post-CRT maintenance, in patients who mount on-treatment activation without catastrophic lymphodepletion. This is a mechanistically motivated hypothesis, not an inference from existing results. Testing needs a factorial or biomarker-stratified trial. We also propose a temporal biomarker framework spanning baseline-predictive, on-treatment early-response, and post-treatment residual-disease markers, graded by evidence and offered as a research agenda. For each stage we name the design that would qualify or refute it. Stage 1 needs registered analysis of archival trial tissue. Stage 2 needs a nested correlative sub-study with prespecified effect modifiers. Stage 3 needs a blinded, prespecified prognostic cohort. We propose, as a hypothesis for prospective testing, that response to CRT\u2013ICI may depend less on any single baseline feature than on whether a patient completes the dynamic transition from viral-antigen exposure through antigen presentation and T-cell recruitment to durable surveillance.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1947595","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:43:03Z","timestamp":1788417783000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune remodeling during cervical cancer chemoradiotherapy: temporal biomarkers and the timing of checkpoint blockade"],"prefix":"10.3389","volume":"17","author":[{"given":"Chenguang","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Affiliated Xuancheng Hospital of Wannan Medical University","place":["Xuancheng, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Affiliated Xuancheng Hospital of Wannan Medical University","place":["Xuancheng, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Affiliated Xuancheng Hospital of Wannan Medical University","place":["Xuancheng, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Affiliated Xuancheng Hospital of Wannan Medical University","place":["Xuancheng, Anhui, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xialing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, 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