The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Cancers, Год журнала: 2020, Номер 12(10), С. 2983 - 2983

Опубликована: Окт. 15, 2020

Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it imperative to understand role factors affecting responsiveness. In this review, we provide overview on involvement sociological factors, lifestyles metabolic disorders modulating CPI response patients from multiple malignancies. Lifestyle habits including exercise, diet promoted therapeutic responsiveness while alcohol consumption mitigated effect by decreasing mutational burden hampering antigen presentation dendritic cells. Metabolic disorder obesity was recognized enhance PD-1 expression diabetes hypertension were consequences therapy rather than causes. Among sociologic sex race positively influenced effectiveness account increased effector T cell activity ageing impaired functional toxicity. The combined these observed gender, which obese males had most significant CPI. Therefore variables should be carefully considered before treating with optimal outcome.

Язык: Английский

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Sex Differences in Lung Cancer

Cancers, Год журнала: 2023, Номер 15(12), С. 3111 - 3111

Опубликована: Июнь 8, 2023

Sex disparities in the incidence and mortality of lung cancer have been observed since statistics recorded. Social economic differences contribute to sex mortality, but evidence suggests that there are also underlying biological disparity. This review summarizes which could hormones other biologically active molecules, tumor cell genetic differences, immune system its response highlighted. How some these therapies, including cytotoxic, targeted, immuno-therapies, is discussed. We end study with a discussion our perceived future directions identify key how be therapeutically leveraged personalize treatment individual sexes.

Язык: Английский

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Gene regulatory networks reveal sex difference in lung adenocarcinoma

Biology of Sex Differences, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 6, 2024

Lung adenocarcinoma (LUAD) has been observed to have significant sex differences in incidence, prognosis, and response therapy. However, the molecular mechanisms responsible for these disparities not investigated extensively.

Язык: Английский

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Immune checkpoint inhibitors-induced autoimmunity: The impact of gender

Autoimmunity Reviews, Год журнала: 2020, Номер 19(8), С. 102590 - 102590

Опубликована: Июнь 17, 2020

Язык: Английский

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Sex Differences in Bladder Cancer Immunobiology and Outcomes: A Collaborative Review with Implications for Treatment

European Urology Oncology, Год журнала: 2020, Номер 3(5), С. 622 - 630

Опубликована: Сен. 20, 2020

Язык: Английский

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Cardiotoxicity Induced by Immune Checkpoint Inhibitors: A Pharmacovigilance Study From 2014 to 2019 Based on FAERS

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Фев. 12, 2021

This study was to scientifically and systematically explore the association between cardiotoxicity immune checkpoint inhibitors (ICIs) also characterize spectrum of ICI-related cardiac complications. From first quarter 2014 fourth 2019, data from FDA Adverse Event Reporting System database were selected conduct disproportionality analysis. odds ratios information components used evaluate signal after statistical shrinkage transformation. In total, 7,443,137 cases 36,326,611 drug-adverse event pairs collected, among which 9,271 identified be related ICI-induced cardiotoxicities. The number male patients much higher than that females (5,579 vs. 3,031) males presented a slightly reporting frequency in general, statistically significant (ROR = 1.04, 95%CI: 0.99–1.09, p < 0.001). Simultaneously, proportion serious or life-threatening outcomes significantly 1.05, 0.96–1.15, Importantly, ICIs associated with over-reporting frequencies cardiotoxicities general (ROR025 1.06, IC025 0.08). PD-1 PD-L1 found adverse events, corresponding ROR025 0.08, respectively, while anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) some specific events rather common events. induced by mostly differed individual agents, but demonstrated features. Dyspnea ( N 2,527, 21.25%), myocarditis 614, 5.16%), atrial fibrillation 576, 4.84%), failure 476, 4.00%), pericardial effusion 423, 3.56%) top five reported database. Among them, only one caused all strong value high risk, warranting further attention. Overall, this investigation mainly showed profile ICIs, varied different ICI therapies, shared similarities symptoms such as myocarditis. Therefore, it is vital urgent recognize manage cardiotoxicities, known frequently occur clinical practice, at earliest point.

Язык: Английский

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Effect of sex on the efficacy of patients receiving immune checkpoint inhibitors in advanced non‐small cell lung cancer

Cancer Medicine, Год журнала: 2019, Номер 8(8), С. 4023 - 4031

Опубликована: Июнь 4, 2019

Immune checkpoint inhibitors (ICIs) have shown promising efficacy in the treatment of non-small cell lung cancer (NSCLC). Sex-associated dimorphism immune system response is acknowledged, but effect patients' sex on ICIs as NSCLC still remains controversial. The present study was conducted to investigate difference patients receiving according sex. A total 9583 involved 6567 men and 3016 women with advanced from 15 randomized controlled trials were included this study. An overall survival (OS) benefit illustrated both male (HR 0.76, 95% CI 0.71-0.82) female 0.73, 0.58-0.91) patients, a progression-free (PFS) also found 0.67, 0.58-0.77) 0.56-0.95) NSCLC. Both PD-1/PD-L1 alone plus chemotherapy significantly improved OS PFS patients. Whereas females, PD-1 or monotherapy benefited not PFS, PD-L1 combination therapy prolonged OS. No CTLA-4 inhibitors. current indicated that magnitude sex-dependent seemed obtain more consistent favorable outcomes than

Язык: Английский

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Exploring the Impact of the Obesity Paradox on Lung Cancer and Other Malignancies

Cancers, Год журнала: 2022, Номер 14(6), С. 1440 - 1440

Опубликована: Март 11, 2022

There is a paradoxical relationship between obesity, as measured by BMI, and many types of cancer, including non-small-cell lung cancer. Obese cancer patients have been shown to fare better than their non-obese counterparts. To analyze the multifaceted effects obesity on oncologic outcomes, we reviewed literature paradox, methods measure adiposity, obesity-related derangements in immunology metabolism, impact confounding variables such gender, smoking, concomitant medications statins metformin. We analyzed how these aspects may contribute paradox outcomes with focus concluded that use BMI adiposity limited should be replaced method can differentiate abdominal obesity. also metabolic immunologic caused paradox. Medications, smoking are additional further research needs performed solidify mechanisms.

Язык: Английский

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Regulating Histone Deacetylase Signaling Pathways of Myeloid-Derived Suppressor Cells Enhanced T Cell-Based Immunotherapy

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Янв. 24, 2022

Immunotherapy has emerged as a promising approach to combat immunosuppressive tumor microenvironment (TME) for improved cancer treatment. FDA approval the clinical use of programmed death receptor 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors revolutionized T cell-based immunotherapy. Although only few patients respond this treatment due several factors including accumulation cells in TME. Several within TME such regulatory cells, myeloid and cancer-associated fibroblast inhibit activation function promote progression. The roles epigenetic modifiers histone deacetylase (HDAC) have long been investigated but little is known about their impact on immune cells. Recent studies showed inhibiting HDAC expression myeloid-derived suppressor (MDSCs) promoted differentiation less suppressive reduced effect upregulated PD-1 or PD-L1 level sensitizing tumor-bearing mice anti-PD-1/PD-L1 antibodies. Herein we discuss how MDSCs could circumvent drawbacks checkpoint improve Furthermore, highlighted current challenges future perspectives regulating effective

Язык: Английский

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Sex-biased adaptive immune regulation in cancer development and therapy

iScience, Год журнала: 2022, Номер 25(8), С. 104717 - 104717

Опубликована: Июль 4, 2022

The cancer research field is finally starting to unravel the mystery behind why males have a higher incidence and mortality rate than females for nearly all types of non-reproductive systems. Here, we explain how sex - specifically chromosomes hormones drives differential adaptive immunity across immune-related disease states including cancer, are consequently more predisposed tumor development. We highlight emerging data on roles cell-intrinsic androgen receptors in driving CD8

Язык: Английский

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