Effect of time‐of‐day nivolumab and stereotactic body radiotherapy in metastatic head and neck squamous cell carcinoma: A secondary analysis of a prospective randomized trial DOI
James Janopaul‐Naylor, Lillian Boe, Yao Yu

et al.

Head & Neck, Journal Year: 2024, Volume and Issue: 46(9), P. 2292 - 2300

Published: May 24, 2024

Abstract Background Prior work documented circadian rhythm impacts on efficacy and toxicity of cancer therapies. Methods Secondary analysis prospective, phase II trial metastatic HNSCC randomized to nivolumab+/−SBRT. Used cutoffs 1100 1630. Timing classified by first infusion or majority SBRT (e.g., PM defined two three fractions after 1630). Results Of 62 patients, there was no significant difference in median PFS between AM nivolumab ( n = 7, 175 days), 21, 58 Mid‐Day 34, 67 days; p 0.8). There with 4, 78 13, 111 15, 63 Grade 3–4 ORR. Sensitivity analyses other timepoints were negative. Conclusions Further may elucidate select tumors, therapies; however, we found effect this study.

Language: Английский

Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation DOI Creative Commons
Meng‐Ling Wu,

Qianrui Huang,

Yao Xie

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 12, 2022

Abstract Immune checkpoint molecules are promising anticancer targets, among which therapeutic antibodies targeting the PD-1/PD-L1 pathway have been widely applied to cancer treatment in clinical practice and great potential. However, this is greatly limited by its low response rates certain cancers, lack of known biomarkers, immune-related toxicity, innate acquired drug resistance, etc. Overcoming these limitations would significantly expand applications blockade improve rate survival time patients. In present review, we first illustrate biological mechanisms immune checkpoints their role healthy system as well tumor microenvironment (TME). The inhibits effect T cells TME, turn regulates expression levels PD-1 PD-L1 through multiple mechanisms. Several strategies proposed solve anti-PD-1/PD-L1 treatment, including combination therapy with other standard treatments, such chemotherapy, radiotherapy, targeted therapy, anti-angiogenic immunotherapies even diet control. Downregulation TME via pharmacological or gene regulation methods improves efficacy treatment. Surprisingly, recent preclinical studies shown that upregulation also blockade. Immunotherapy a strategy provides novel insight into applications. This review aims guide development more effective less toxic immunotherapies.

Language: Английский

Citations

299
Neutrophil phenotypes and functions in cancer: A consensus statement DOI Creative Commons

Daniela F. Quail,

Borko Amulic, Monowar Aziz

et al.

The Journal of Experimental Medicine, Journal Year: 2022, Volume and Issue: 219(6)

Published: May 6, 2022

Neutrophils are the first responders to infection and inflammation thus a critical component of innate immune defense. Understanding behavior neutrophils as they act within various inflammatory contexts has provided insights into their role in sterile infectious diseases; however, field cancer is comparatively young. Here, we summarize key concepts current knowledge gaps related diverse roles throughout progression. We discuss sources neutrophil heterogeneity provide recommendations on nomenclature for states that distinct maturation activation. address discrepancies literature highlight need technical standards ought be considered between laboratories. Finally, review emerging questions biology immunity cancer. Overall, emphasize more population than previously appreciated may present novel unexplored opportunities treat

Language: Английский

Citations

208
Circadian rhythms and cancers: the intrinsic links and therapeutic potentials DOI Creative Commons
Li Zhou, Zhe Zhang, Edouard C. Nice

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: March 4, 2022

The circadian rhythm is an evolutionarily conserved time-keeping system that comprises a wide variety of processes including sleep-wake cycles, eating-fasting and activity-rest coordinating the behavior physiology all organs for whole-body homeostasis. Acute disruption may lead to transient discomfort, whereas long-term irregular will result in dysfunction organism, therefore increasing risks numerous diseases especially cancers. Indeed, both epidemiological experimental evidence has demonstrated intrinsic link between dysregulated cancer. Accordingly, rapidly understanding molecular mechanisms rhythms opening new options cancer therapy, possibly by modulating clock. In this review, we first describe general regulators their functions on addition, provide insights into underlying how several types (including sleep-wake, eating-fasting, activity-rest) can drive progression, which expand our development from clock perspective. Moreover, also summarize potential applications treatment, optional therapeutic strategy patients.

Language: Английский

Citations

91
Foundations of circadian medicine DOI Creative Commons
Achim Kramer, Tanja Lange, Claudia Spies

et al.

PLoS Biology, Journal Year: 2022, Volume and Issue: 20(3), P. e3001567 - e3001567

Published: March 24, 2022

The circadian clock is an evolutionarily highly conserved endogenous timing program that structures physiology and behavior according to the time of day. Disruption rhythms associated with many common pathologies. emerging field medicine aims exploit mechanisms clock–disease interaction for clinical diagnosis, treatment, prevention. In this Essay, we outline principle approaches medicine, highlight development in selected areas, point out open questions challenges. Circadian has unambiguous health benefits over standard care but rarely utilized. It biology become integrated part translational research.

Language: Английский

Citations

70
Decoding the tumor microenvironment with spatial technologies DOI
Logan A. Walsh,

Daniela F. Quail

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 1982 - 1993

Published: Nov. 27, 2023

Language: Английский

Citations

60
Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis DOI Creative Commons
Thierry Landre, Abdoulaye Karaboué, Zachary S. Buchwald

et al.

ESMO Open, Journal Year: 2024, Volume and Issue: 9(2), P. 102220 - 102220

Published: Jan. 21, 2024

Background

Immune checkpoint inhibitors (ICIs) have become the standard of care for numerous malignancies. Emerging evidence suggests that time day (ToD) ICI administration could impact outcomes patients with cancer. The consistency ToD effects on efficacy awaits initial evaluation.

Materials and methods

This meta-analysis integrates progression-free survival (PFS) overall (OS) data from studies a defined ‘cut-off' ToD. Hazard ratios (HRs) [95% confidence interval (CI)] an earlier progression or death according to ‘early' ‘late' ICIs were collected each report pooled.

Results

Thirteen involved 1663 (Eastern Cooperative Oncology Group performance status 0-1, 83%; males/females, 67%/33%) non-small-cell lung cancer (47%), renal cell carcinoma (24%), melanoma (20%), urothelial (5%), esophageal (4%). Most received anti-programmed protein 1 death-ligand (98%), small proportion also anti-cytotoxic T-lymphocyte-associated 4 (anti-CTLA-4) (18%). cut-offs 13:00 14:00 (i.e. median infusion time), six studies, 16:00 16:30 reported threshold weaker vaccination responses) seven studies. Pooled analyses revealed early groups had longer OS (HR 0.50, 95% CI 0.42-0.58; P < 0.00001) PFS 0.51, 0.42-0.61; compared late groups.

Conclusions

Patients selected metastatic cancers seemed largely benefit infusions, which is consistent circadian mechanisms in immune-cell functions trafficking. Prospective randomized trials are needed establish recommendations optimal timing ICI-based therapies.

Language: Английский

Citations

25
Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade DOI
Bridget M. Fortin, Shannon M. Pfeiffer, Jacob Insua‐Rodríguez

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(7), P. 1257 - 1269

Published: May 28, 2024

Language: Английский

Citations

22
Circadian regulation of cancer stem cells and the tumor microenvironment during metastasis DOI
Yu Wang, Rajesh Narasimamurthy, Meng Qu

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(4), P. 546 - 556

Published: April 23, 2024

Language: Английский

Citations

19
Time-Dependent Efficacy of Checkpoint Inhibitor Nivolumab: Results from a Pilot Study in Patients with Metastatic Non-Small-Cell Lung Cancer DOI Open Access
Abdoulaye Karaboué,

T. Collon,

Ida Pavese

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(4), P. 896 - 896

Published: Feb. 11, 2022

Prior experimental and human studies have demonstrated the circadian organization of immune cells' proliferation, trafficking, antigen recognition destruction. Nivolumab targets T(CD8) cells, functions, trafficking which are regulated by clocks, hence suggesting possible daily changes in nivolumab's efficacy. Worse progression-free survival (PFS), overall (OS) were reported for malignant melanoma patients receiving more than 20% their checkpoint inhibitor infusions after 16:30 as compared to earlier day.Consecutive metastatic non-small-cell cancer (NSCLC) received nivolumab (240 mg iv q 2 weeks) at a time that was 'randomly' allocated each course on logistical basis day-hospital coordinators. The median all administrations computed patient. study population split into two timing groups based upon value treatment times patients. CTCAE-toxicity rates, iRECIST-tumor responses, PFS OS according timing. curves hazard ratios (HR) major categories characteristics. Multivariable sensitivity analyses also performed.The accrued 95 stage-IV NSCLC (PS 0-1, 96%), aged 41-83 years. majority occurred between 9:27 12:54 48 ('morning' group) 12:55 17:14 other 47 ('afternoon' group). Median (95% CL) 11.3 months (5.5-17.1) 'morning' group 3.1 (1.5-4.6) 'afternoon' one (p < 0.001). 34.2 (15.1-53.3) 9.6 (4.9-14.4) one, respectively identified significant predictor longer OS, with respective HR values 0.26 (0.11-0.58) 0.17 (0.08-0.37). effect consistent across patient subgroups tested.Nivolumab nearly four effective following dosing this cohort Prospective timing-studies needed minimize risk resistance maximize benefits from inhibitors.

Language: Английский

Citations

64
Chronotherapy: Circadian Rhythms and Their Influence in Cancer Therapy DOI Open Access
Ana Amiama-Roig, Eva M. Verdugo‐Sivianes, Amancio Carnero

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(20), P. 5071 - 5071

Published: Oct. 17, 2022

Living organisms present rhythmic fluctuations every 24 h in their behavior and metabolism to anticipate changes the environment. These are controlled by a very complex molecular mechanism, circadian clock, that regulates expression of multiple genes ensure right functioning body. An individual’s system is altered during aging, this related numerous age-associated pathologies other alterations could contribute development cancer. Nowadays, there an increasing interest understanding how rhythms be used treatment Chronotherapy aims understand impact biological have on response therapy optimize its action, maximize health benefits minimize possible adverse effects. Clinical trials so far confirmed optimal timing with chemo or immunotherapies decrease drug toxicity increase efficacy. Instead, chronoradiotherapy seems treatment-related symptoms rather than tumor progression patient survival. In addition, potential therapeutic targets within clock also been identified. Therefore, results application chronotherapy cancer until now challenging, feasible, applied clinical practice improve without additional costs. However, different limitations variables such as age, sex, chronotypes, among others, should overcome before can really put into practice.

Language: Английский

Citations

48