ArticleMolecular cancer research : MCR2022
Diurnal Expression of PD-1 on Tumor-Associated Macrophages Underlies the Dosing Time-Dependent Antitumor Effects of the PD-1/PD-L1 Inhibitor BMS-1 in B16/BL6 Melanoma-Bearing Mice.
Article in Molecular cancer research : MCR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Time-of-Day Immunotherapy Administration and Outcomes in Advanced Cancers: A Systematic Review and Meta-Analysis.JAMA network open · 2026Pooled it
- Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis.ESMO open · 2024Pooled it
- Morning versus afternoon administration of immune checkpoint inhibitors in metastatic non-small-cell lung cancer.Journal for immunotherapy of cancer · 2026Trial
- Circadian timing of first-line chemoimmunotherapy is associated with survival in extensive-stage small cell lung cancer.Oncoimmunology · 2026Article
- Unlocking the clock: a systematic review and meta-analysis on optimizing immune checkpoint inhibitor timing for advanced solid tumors.British journal of cancer · 2026Article
- The circadian architecture of tumor immunity: mechanistic insights and treatment strategies.Biomarker research · 2026Review
- Circadian Rhythms in Colorectal Cancer: Recent Advances in Development and Treatment.Journal of clinical medicine research · 2026Review
- Timing of immune checkpoint inhibitors infusion and prognosis in recurrent/metastatic nasopharyngeal carcinoma: a single-center, retrospective study.Cancer immunology, immunotherapy : CII · 2026Article
- Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors.BMC cancer · 2026Article
- Circadian engineering of in vivo CAR T cell therapy for precision oncology.NPJ precision oncology · 2026Review
- Article
- Therapeutic Strategies Targeting the Kidney-Liver-Immune-Heart Network: Circadian and Mechanosensory Pathways in CKD-Associated Cardiac Injury.International journal of molecular sciences · 2026Review
- C-X-C chemokine receptor CXCR4 mediates diurnal changes in the aggregation and dispersion of CD8International journal of cancer · 2026Article
- Day/night variations of myeloid and lymphoid cell subsets in the murine inguinal lymph node.FEBS open bio · 2026Article
- Temporal dynamics in cancer immunotherapy: the interplay between circadian rhythms, tumor microenvironment, and immune checkpoint blockade.Journal of the National Cancer Center · 2026Review
- Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment.Acta biochimica et biophysica Sinica · 2026Review
- Chrono-immunotherapy's current and future optimization strategies: immunotherapy timing in line with the circadian rhythm brings longer survival benefits.Frontiers in immunology · 2026Review
- Synchronizing immunity with time: unlocking the potential of chrono-immunotherapy in cancer.Frontiers in immunology · 2026Review
- Early time-of-day infusion of PD-1 inhibitor improves prognosis in advanced gastric cancer: a multicenter real-world study.Frontiers in immunology · 2026Article
- Impact of time-of-day and timing interval of neoadjuvant immunotherapy and chemotherapy infusions among patients with operable NSCLC using the inverse probability of treatment weighting method: a dual-center, retrospective study.Frontiers in immunology · 2026Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death 1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAM), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1-expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a NF-κB response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-κB-induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the antitumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors. IMPLICATIONS: Selecting the most appropriate dosing time of PD-1/PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.