{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:04:47Z","timestamp":1784725487897,"version":"3.55.0"},"reference-count":62,"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\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Innate immune signals encode functional instructions through temporal patterns such as oscillation frequency and duration\u2014a principle validated at the single-cell level. Yet clinical evaluation of host responses in tumor immunotherapy remains dominated by \u201chow strongly\u201d the immune system is activated, while the waveform of the response\u2014how it unfolds and when it resolves\u2014is largely overlooked. This disconnect raises unresolved questions: why can tumor progression persist despite intense inflammation, and why is fixed-interval maintenance not universally effective? Intravesical BCG instillation offers a way forward: each instillation is a controlled stimulus, voided urine provides a noninvasive sampling window, and oncological plus bladder-function outcomes form a \u201ccontrolled stimulus\u2013noninvasive sampling\u2013dual-endpoint\u201d closed loop. Using this model, we propose a hypothesis organized around two observation levels. The fundamental unit is the single\u2212instillation single\u2212cytokine waveform\u2014the complete concentration-time curve of one cytokine following one BCG dose; the second is the longitudinal waveform trajectory, which captures how such waveforms evolve across repeated instillations. Both levels reside at a mesoscopic interface between single-cell signaling dynamics and macro-scale clinical outcomes. Our central hypothesis is that temporal features of a single-instillation single-cytokine waveform\u2014time-to-peak, elimination half-life, and decay morphology\u2014carry predictive information independent of peak amplitude. Distinct waveform shapes may differentially instruct adaptive immune quality, while the decay phase defines the time window for immune homeostasis restoration, thus providing a biological rationale for individualized instillation timing. If validated, this framework would expand the evaluation paradigm for intravesical immunotherapy from an \u201camplitude\u201d dimension to a dual \u201camplitude + waveform\u201d paradigm.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1904049","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:11:58Z","timestamp":1784722318000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding the temporal dimension of innate immunity in intravesical BCG therapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Xuewen","family":"Diao","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Guizhou University of Traditional Chinese Medicine","place":["Guiyang, China"]},{"name":"Department of Urology and Andrology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine","place":["Guiyang, 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