Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Dec. 18, 2024
Circadian rhythms in the immune system and anti-tumor responses are underexplored cancer immunotherapy. Despite success of checkpoint inhibitors (ICIs) treating advanced biliary tract cancers (BTCs), not all patients benefit. This study examined whether timing ICI administration affects outcomes BTC patients.
Language: Английский
Cell, Journal Year: 2024, Volume and Issue: 187(11), P. 2690 - 2702.e17
Published: May 1, 2024
The quality and quantity of tumor-infiltrating lymphocytes, particularly CD8+ T cells, are important parameters for the control tumor growth response to immunotherapy. Here, we show in murine human cancers that these exhibit circadian oscillations, driven by both endogenous clock leukocytes rhythmic leukocyte infiltration, which depends on endothelial cells microenvironment. To harness rhythms therapeutically, demonstrate efficacy chimeric antigen receptor cell therapy immune checkpoint blockade can be improved adjusting time treatment during day. Furthermore, time-of-day-dependent signatures models predict overall survival patients with melanoma correlate anti-PD-1 therapy. Our data functional significance dynamics microenvironment suggest importance leveraging features improving future clinical trial design patient care.
Language: Английский
Citations
61
Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15
Published: Jan. 9, 2025
Despite enormous progress, advanced cancers are still one of the most serious medical problems in current society. Although various agents and therapeutic strategies with anticancer activity known used, they often fail to achieve satisfactory long-term patient outcomes survival. Recently, immunotherapy has shown success patients by harnessing important interactions between immune system cancer. However, many these therapies lead frequent side effects when administered systemically, prompting treatment modifications or discontinuation or, severe cases, fatalities. New approaches like intratumoral immunotherapy, characterized reduced effects, cost, systemic toxicity, offer promising prospects for future applications clinical oncology. In context locally metastatic cancer, combining diverse immunotherapeutic other targeting multiple cancer hallmarks appears crucial. Such combination hold promise improving survival promoting a sustained response. This review aims provide overview approaches, specifically focusing on administration drugs cancers. It also explores integration modalities maximize Additionally, summarizes recent advances discusses novel outlining directions field.
Language: Английский
Citations
2
Research, Journal Year: 2025, Volume and Issue: 8
Published: Jan. 1, 2025
The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis cancer progression. Aging well-established primary risk for while disruptions rhythms are intricately associated with progression of various tumors. Moreover, itself disrupts leading to physiological changes that may accelerate development. Despite these connections, specific interplay processes their collective impact on remains inadequately explored literature. In this review, we systematically explore influence We discuss how core genes tumor prognosis, highlighting shared hallmarks such genomic instability, cellular senescence, chronic inflammation. Furthermore, examine aging, focusing crosstalk contributes tumorigenesis, proliferation, apoptosis, well metabolism stability. By elucidating common pathways linking review provides new insights into pathophysiology identifies potential therapeutic strategies. propose targeting regulation could pave way novel treatments, including chronotherapy antiaging interventions, which offer important benefits clinical management cancer.
Language: Английский
Citations
2
Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(3), P. e008011 - e008011
Published: March 1, 2024
Background Recent studies have demonstrated that earlier time-of-day infusion of immune checkpoint inhibitors (ICIs) is associated with longer progression-free survival (PFS) and overall (OS) among patients metastatic melanoma non-small cell lung cancer. These data are in line growing preclinical evidence the adaptive response may be more effectively stimulated day. We sought to determine impact ICI infusions on outcomes renal carcinoma (mRCC). Methods The treatment records all stage IV RCC who began therapy within a multicenter academic hospital system between 2015 2020 were reviewed. associations proportion administered prior noon (denoting morning infusions) PFS OS evaluated using univariate multivariable Cox proportional hazards regression. Results In this study, 201 mRCC (28% women) received ICIs followed over median 18 months (IQR 5–30). age at time initiation was 63 years 56–70). 101 (50%) ≥20% their (Group A) 100 <20% B). Across two comparison groups, initial agents consisted nivolumab (58%), plus ipilimumab (34%), pembrolizumab (8%). On analysis, Group A had compared those B (PFS HR 0.67, 95% CI 0.48 0.94, P univar =0.020; 0.57, 0.34 0.95, =0.033). significant findings persisted following adjustment for age, sex, performance status, International Metastatic Database Consortium risk score, pretreatment lactate dehydrogenase, histology, presence bone, brain, liver metastases 0.70, 0.50 0.98, multivar =0.040; 0.33 =0.043). Conclusions Patients benefit from receipt ICIs. Our consistent established mechanisms chrono-immunology, as well preceding analogous Additional prospective randomized trials warranted.
Language: Английский
Citations
14
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
Citations
4
Immunology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 8, 2025
ABSTRACT Circadian rhythm is a physiological process that oscillates in 24 h cycle. It has complex connection with the function of human immune system and even development tumours. Previous studies demonstrated time‐dependent effects chemotherapy radiotherapy; however, there are few on timing immunotherapy. Here, we explored differences efficacy checkpoint inhibitors (ICIs) administered at different circadian times non‐small cell lung cancer (NSCLC). C57BL/6N Lewis mice models were constructed. Then, intraperitoneally injected saline or anti‐PD‐1 antibody 7 AM PM, The expression PD‐L1 was detected by flow cytometry, expressions clock gene BMAL1 PER2 polymerase chain reaction (PCR) after treatment. A retrospective analysis conducted patients NSCLC who received ICIs our department from June 2020 to December 2022. Animal experiments showed treated morning slower tumour growth smaller volumes than those afternoon, accompanied increased suppression expression. Retrospective afternoon (after 12:00) had significantly longer progression‐free survival (before (median 16.5 months versus 9.8 months, respectively, p = 0.031, hazard ratio 1.87). These findings suggest immunotherapy may have time dependence, offering novel therapeutic strategy.
Language: Английский
Citations
0
Deutsches Ärzteblatt, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 30, 2025
Citations
0
Chronobiology International, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13
Published: Jan. 31, 2025
Research linking circadian dysregulation to cancer development has received increasing attention recently. However, a comprehensive understanding of research hotspots and trends in this area remains limited. International studies on the rhythms were retrieved downloaded from Web Science database. Bibliometric analysis visualization performed using VOSviewer, CiteSpace, HistCite. Three thousand three hundred eighteen English articles 2004 2024 screened evaluated. The increase publications citations reflected rapid expansion field. Scholars institutions United States have relatively high academic productivity impact. Chronobiology is most popular journal. Key clustering identified six themes: biochemistry molecular biology, physiology immunomodulation, night shift work health effects, physiological mental health, tumor therapy research, oxidative stress cancer-related mechanisms. Keyword burst regulation cells microenvironment as frontiers. role immunotherapy was current hotspot by reference co-citation analysis. This study reveals status predicts future trends. These findings provide new ideas for developing novel prevention treatment strategies.
Language: Английский
Citations
0
EBioMedicine, Journal Year: 2025, Volume and Issue: 113, P. 105607 - 105607
Published: Feb. 20, 2025
Language: Английский
Citations
0
Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 732 - 732
Published: Feb. 21, 2025
In the era of precision medicine, mounting evidence suggests that time therapy administration, or chronotherapy, has a great impact on treatment outcomes. Chronotherapy involves planning timing by considering circadian rhythms, which are 24 h oscillations in behavior and physiology driven synchronized molecular clocks throughout body. The value chronotherapy cancer is currently under investigation, notably effects efficacy side effects. Immune checkpoint inhibitor (ICI) promising treatment. However, many patients still experience disease progression need to stop early due There accumulating day at ICI administered can have substantial effect efficacy. Thus, it important investigate intersections this review, we provide brief overview rhythms context immunity cancer. Additionally, outline current applications for We synthesize 29 studies conducted date examine time-of-day administration therapy, its associated effects, sex differences both also discuss potential mechanisms underlying these observed results. Finally, highlight challenges area future directions research, including chronotherapeutic personalized medicine approach tailors individual patients’ rhythms.
Language: Английский
Citations
0