bims-ciryme Biomed News
on Circadian rhythms and metabolism
Issue of 2026–06–21
two papers selected by
Gabriela Da Silva Xavier, University of Birmingham
  1. Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.
  2. Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors.
  1. Elife. 2026 Jun 15. pii: RP110786. [Epub ahead of print]15
    Nuclear CK1δ as a critical determinant of PER:CRY complex dynamics and circadian period.
    Fidel Emmanuel Serrano, Daniela Marzoll, Bianca Ruppert, Axel C R Diernfellner, Michael Brunner.
      The mammalian circadian clock is governed by a feedback loop in which the transcription activator CLOCK:BMAL1 induces expression of its inhibitors, PERs and CRYs, which form a complex with CK1δ, the main circadian kinase. However, the spatiotemporal dynamics of this feedback loop and the precise role of CK1δ remain incompletely understood. Using an inducible overexpression system, we show that nuclear availability of CK1δ is limited by both rapid nuclear degradation and active export of unassembled kinase, while cytoplasmic kinase is readily available for association with PERs. We demonstrate that CK1δ-mediated phosphorylation may disrupt PER2-CRY1 interaction, thereby resulting in cytoplasmic PER2 dimers containing substoichiometric amounts of CRY1. Analysis of endogenous PER2 localization in the context of an intact circadian clock reveals that PER2 accumulates in the cytoplasm late in the circadian cycle. Based on these findings, we propose that cytoplasmic accumulation of PER:CRY:CK1δ complexes contributes to the clearance of nuclear PER2, while the CK1δ-dependent release of CRY1 into the nucleus may sustain CLOCK:BMAL1 repression on DNA, supporting the transition from the early to the late repressive phase.
    Keywords:  CK1; CRY1; PER2; biochemistry; chemical biology; circadian clock; human
    DOI:  https://doi.org/10.7554/eLife.110786
  2. BMC Cancer. 2026 Jun 19.
    Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors.
    Eli M Soyfer, Benjamin J Lee, Abraham J Qavi, Selma Masri, Angela G Fleischman, Farshid Dayyani.
       BACKGROUND: The circadian clock regulates tumor-immune interactions in a time-of-day-dependent manner, yet whether this translates to a clinically meaningful benefit across diverse solid tumors in real-world populations remains unclear.
    METHODS: We retrospectively analyzed 969 patients receiving anti-PD-1 or anti-PD-L1 therapy at UCI Health between 2018 and 2022. Patients were classified as early (before 12 PM) or late (12 PM or after) based on infusion time. The primary outcome was disease control rate (DCR), defined as complete response (CR), partial response (PR), or stable disease (SD) per RECIST criteria. Unadjusted comparisons used the Pearson chi-square test. Multivariable logistic regression adjusting for disease stage, age, and ethnicity was performed in 806 patients with complete covariate data. Propensity score-matched analyses and sensitivity analyses using alternative exposure definitions were conducted.
    RESULTS: Early infusion was associated with significantly higher DCR compared with late infusion (49% vs. 40%, p = 0.007). This association persisted after multivariable adjustment (adjusted OR 1.18, 95% CI 1.02-1.38, p = 0.024). The effect was directionally consistent across subgroups defined by sex, age, stage, and ICI agent. In ethnicity-stratified analyses, the association was significant among non-Hispanic patients (adjusted OR 1.18, 95% CI 1.02-1.39) but was indeterminate among Hispanic patients due to limited sample size (adjusted OR 1.18, 95% CI 0.84-1.65); the ethnicity-by-TOD interaction term was non-significant (p = 0.958). Sensitivity analyses using alternative exposure definitions and propensity score matching yielded consistent results.
    CONCLUSIONS: In a large, heterogeneous real-world cohort spanning multiple tumor types and a diverse patient population, early ICI administration was independently associated with higher DCR. These findings support a chronotherapeutic effect of ICI timing and underscore DCR as a sensitive endpoint for its detection. Prospective validation across tumor types and demographic subgroups is warranted.
    Keywords:  Circadian rhythm; Disease control rate; Immune checkpoint inhibitors; Real-world evidence; Time-of-day
    DOI:  https://doi.org/10.1186/s12885-026-16364-w
This page is being maintained by Thomas Krichel. It was last updated on 2026‒06‒22 at 9:20.