What question did this study set out to answer?

To investigate how circadian rhythms influence heat shock protein (HSP) expression and anti-tumor immunity during localized hyperthermia.

April 5, 2026

Abstract 1574: Chronotherapy of hyperthermia: Circadian rhythm governs HSP expression and modulates anti-tumor immunity

Key Points

To investigate how circadian rhythms influence heat shock protein (HSP) expression and anti-tumor immunity during localized hyperthermia.
Utilized murine tumor models to test localized hyperthermia at different times of day.
Analyzed expression levels of heat shock proteins and damage-associated molecular patterns post-treatment.
Examined infiltration of CD8+ T cells in tumor tissues.
Conducted genetic ablation of core circadian clock proteins to assess their regulatory role.
Evaluated the effectiveness of hyperthermia timing in combination with anti-CTLA-4 antibody.
HSP expression showed significant circadian variation, peaking in the afternoon and reducing at night.
Nighttime hyperthermia resulted in greater release of HMGB1 and ATP from tumor tissues.
Enhanced infiltration of CD8+ T cells was observed with nighttime hyperthermia.
Nighttime hyperthermia significantly boosted anti-tumor effects when combined with anti-CTLA-4 therapy.

Abstract

Abstract Background: Heat shock protein (HSP) expression is a key mechanism underlying hyperthermia-induced anti-tumor immunity. However, whether HSP expression exhibits circadian rhythmicity and how this impacts therapeutic efficacy remains unclear. Methods: Murine tumor models received localized hyperthermia at different times of day (specifically comparing afternoon and nighttime). Core circadian clock proteins (e.g., Bmal1 or Clock) were genetically ablated. Tumor tissues were analyzed for: (1) HSP expression levels post-hyperthermia; (2) release of damage-associated molecular patterns (DAMPs), including HMGB1 and ATP; (3) infiltration of CD8+ T cells. The effect of hyperthermia timing on treatment efficacy, both alone and in combination with anti-CTLA-4 antibody, was evaluated. Results: HSP expression induced by hyperthermia showed significant circadian variation: it was highest when hyperthermia was administered in the afternoon and lowest when administered at nighttime. Genetic ablation of core circadian clock proteins abolished this time-dependent difference in HSP expression, confirming the critical regulatory role of the biological clock. Compared to afternoon hyperthermia, nighttime hyperthermia triggered significantly greater release of immunogenic DAMPs (HMGB1, ATP) from tumor tissue and induced markedly enhanced infiltration of CD8+ T cells.Crucially, nighttime hyperthermia demonstrated a significantly stronger synergistic anti-tumor effect when combined with anti-CTLA-4 immune checkpoint blockade therapy. Conclusion: The circadian rhythm profoundly influences the immunogenic effects of hyperthermia by regulating HSP expression. Although inducing lower HSP levels, nighttime hyperthermia is more effective at releasing immunogenic DAMPs (HMGB1, ATP), promoting CD8+ T cell infiltration, and potently enhancing the efficacy of anti-CTLA-4 therapy. This study identifies timing of hyperthermia administration (specifically nighttime) as a critical factor for optimizing immunogenic cell death and augmenting the effectiveness of combined immunotherapy. Citation Format: Tingting Lin, Chunyan Lin, Zhilian Zhou, Shan Li, Lifeng Zhu, Yingming Sun, . Chronotherapy of hyperthermia: Circadian rhythm governs HSP expression and modulates anti-tumor immunity abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1574.

Mark Helpful

Bookmark

Relay