The impact of sex and gender on immunotherapy outcomes

Biology of Sex Differences, Год журнала: 2020, Номер 11(1)

Опубликована: Май 4, 2020

Abstract Immunotherapies are often used for the treatment, remission, and possible cure of autoimmune diseases, infectious cancers. Empirical evidence illustrates that females males differ in outcomes following use biologics treatment e.g., rheumatoid arthritis (RA), influenza, solid tumor Females tend to experience more adverse reactions than a class referred as immunotherapies. For immunotherapies aimed at stimulating an immune response, influenza vaccines, develop greater responses may efficacy males. In contrast, repress necrosis factor (TNF) inhibitors RA or checkpoint melanoma, is reportedly females. Despite these differences, discrepancies reporting differences between exist, with have been historically excluded from biomedical clinical studies. There critical need research addresses biological (i.e., sex) well sociocultural gender) causes male-female disparities immunotherapy responses, toxicities, outcomes. One-size-fits-all approaches will not work, sex/gender contribute variable success, including adherence, settings.

Язык: Английский

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Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications

Nature reviews. Cancer, Год журнала: 2024, Номер 24(5), С. 338 - 355

Опубликована: Апрель 8, 2024

Язык: Английский

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Outcome differences by sex in oncology clinical trials

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Март 23, 2024

Abstract Identifying sex differences in outcomes and toxicity between males females oncology clinical trials is important has also been mandated by National Institutes of Health policies. Here we analyze the Trialtrove database, finding that, strikingly, only 472/89,221 (0.5%) had curated post-treatment comparisons. Among 288 with comparisons survival, outcome, or response, 16% report having statistically significant better survival outcome while 42% reported significantly response for females. The strongest are EGFR inhibitors lung cancer rituximab non-Hodgkin’s lymphoma (both favoring females). 44 side effect comparisons, more lesser effects ( N = 22) than 13). Thus, statistical sexes rarely reported, exist. These considerable highlight need reporting thoroughly going forward.

Язык: Английский

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Sex Differences in Cancer Immunotherapy Efficacy, Biomarkers, and Therapeutic Strategy

Molecules, Год журнала: 2019, Номер 24(18), С. 3214 - 3214

Опубликована: Сен. 4, 2019

Sex differences in innate and adaptive immune responses are known, women generally mount a stronger response than men. Cancer immunotherapy, represented by checkpoint inhibitors (ICIs), has revolutionized the treatment of cancer, sex cancer immunotherapy just starting to be revealed. Here, we summarize recent research progress concerning efficacy. On their own, ICIs tend more effective male patients compared with female patients, while combined chemotherapy patients. Male tumors usually antigenic tumors, this is reflected increased number tumor mutations germline antigens. The biomarker mutational burden (TMB), which reflects antigenicity, at predicting for lung In review, propose different therapeutic strategies sexes: For environment should enhanced, whereas antigenicity enhanced.

Язык: Английский

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Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US Food and Drug Administration adverse events reporting system

Journal for ImmunoTherapy of Cancer, Год журнала: 2019, Номер 7(1)

Опубликована: Ноя. 6, 2019

Immune-checkpoint inhibitors (ICIs) emerged as a novel class of drugs for the treatment broad spectrum malignancies. ICIs can produce durable antitumor responses but they are also associated with immune-related adverse events (irAEs). Endocrinopathies have reported one most common irAEs ICIs.This study aimed to quantify association endocrine (AEs) and ICI therapy characterize profiles ICI-related complications from real-world practice. Data first quarter 2014 2019 in FDA Adverse Event Reporting System (FAERS) database were gathered conduct disproportionality analysis. The definition AEs relied on preferred terms (PTs) provided by Medical Dictionary Regulatory Activities (MedDRA). Two signal indices based statistical shrinkage transformation, reporting odds ratios (ROR) information component (IC), used evaluate correlations between events. For ROR, it was defined if lower limit 95% confidence interval (ROR025) more than one, at least 3 cases. IC, end IC (IC025) exceeding zero deemed statistically significant.A total 29,294,336 records involved, among these 6260 related after identified. In general, male had slightly frequencies ICIs-related endocrinopathies compared female not significant (ROR = 0.98 95%CI: 0.93-1.04) difference varied several AEs. Notably, significantly over-reporting complications, corresponding IC025 2.49 ROR025 5.99. monotherapy, three strategies (anti-PD-1, anti-PD-L1 anti-CTLA-4) all increasing Different when anti-CTLA-4 anti-PD-1/PD-L1 medications toxicities, ROR 1.68 (95%CI 1.55-1.83), 2.54 2.20-2.93), respectively. Combination higher risk monotherapy 2.00, 95%CI 1.89-2.11). When further analysis, differed immunotherapy regimens. Hypothyroidism (N 885,14.14%), adrenal insufficiency(N 730,11.66%), hypophysitis 688,10.99%) hyperthyroidism 472,7.54%) top 4 ranked their frequency immunotherapies.Our pharmacovigilance analysis shows high provoked (especially therapy) reinforced combination therapy. addition, different immunotherapies may result unique distinct profile endocrinopathies. Early recognition management is vital importance clinical

Язык: Английский

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Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2020, Номер 21(12), С. 4414 - 4414

Опубликована: Июнь 21, 2020

Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both tumor microenvironment (TME) at host level. review, we summarize most important immune-metabolic factors how they could be exploited therapeutically. At cellular level, increased concentration extracellular adenosine as well depletion tryptophan uncontrolled activation PI3K/AKT pathway induces immune-tolerant TME, reducing response to ICIs. Moreover, aberrant angiogenesis hypoxic environment by recruiting VEGF, Treg cells immune-suppressive associated macrophages (TAMs). On other hand, such gender body mass index seem affect ICIs, while microbiome composition (and its alterations) modulates development immune-related adverse events. Exploiting these complex mechanisms next goal immunotherapy. The successful strategy date has been combination antiangiogenic drugs which prolonged survival patients with non-small-cell lung cancer (NSCLC) hepatocellular carcinoma (HCC), results from inhibition studies are inconclusive. New exciting strategies include targeting pathway, TAMs microbiota fecal transplantation.

Язык: Английский

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Sex and Gender Disparities in Melanoma

Cancers, Год журнала: 2020, Номер 12(7), С. 1819 - 1819

Опубликована: Июль 7, 2020

Worldwide, the total incidence of cutaneous melanoma is higher in men than women, with some differences related to ethnicity and age and, above all, sex gender. Differences exist respect anatomic localization melanoma, that it more frequent on trunk lower limbs women. A debated issue if-and what extent-melanoma development can be attributed gender-specific behaviors or biologically intrinsic differences. In search for factors responsible divergences, a pivotal role hormones has been observed, although conflicting results indicate involvement other mechanisms. The presence X chromosome numerous miRNAs coding genes playing immunological roles represents another important factor, whose relevance even increased by incomplete random inactivation. Considering known advantages female immune system, different cancer surveillance efficacy was suggested explain disparities. Indeed, complexity this picture emerged when recently developed immunotherapies unexpectedly showed better improvements Altogether, these data support necessity further studies, which consider enrolling balanced number women clinical trials understand obtain actual gender-equitable healthcare.

Язык: Английский

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Clinical trials for COVID-19 should include sex as a variable

Journal of Clinical Investigation, Год журнала: 2020, Номер 130(7), С. 3350 - 3352

Опубликована: Май 11, 2020

The number of COVID-19 cases appears to be comparable between men and women, but the severity disease death is two times greater for than women (1, 2).History, including 1918 influenza pandemic, warned us that male biases in could occur.In this Viewpoint, we focus on biological explanations, with a forward look at why clinicians biomedical researchers should consider sex as variable will affect treatment outcomes COVID-19.There long history not analyzing or reporting differences prophylactic therapeutic infectious diseases.We seek reverse trend call investigators developing testing approaches design studies are inclusive versus female drug responses, immunotherapies, vaccines, nonpharmacological interventions.

Язык: Английский

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“Bridging the Gap” Everything that Could Have Been Avoided If We Had Applied Gender Medicine, Pharmacogenetics and Personalized Medicine in the Gender-Omics and Sex-Omics Era

International Journal of Molecular Sciences, Год журнала: 2019, Номер 21(1), С. 296 - 296

Опубликована: Дек. 31, 2019

. Gender medicine is the first step of personalized and patient-centred care, an essential development to achieve standard goal a holistic approach patients diseases. By addressing interrelation integration biological markers (i.e., sex) with indicators psychological/cultural behaviour gender), gender represents crucial assumption for achieving health-care required in third millennium. However, 'sex' 'gender' are often misused as synonyms, leading frequent misunderstandings those who not deeply involved field. Overall, we have face evidence that biological, genetic, epigenetic, psycho-social, cultural, environmental factors mutually interact defining sex/gender differences, at same time establishing potential unwanted disparities. Prioritizing role physiological pathological processes terms efficient prevention, clinical signs' identification, prognosis definition, therapy optimization. In this regard, omics-approach has become powerful tool identify sex/gender-specific disease markers, benefits also socio-psychological wellbeing each individual, cost-effectiveness National Healthcare systems. "Being male or being female" indeed important from health point view it no longer possible avoid "sex lens" when approaching patients. Accordingly, healthcare must be based on targeted research studies aimed understanding how sex influence across entire life span. The rapid genetic tools molecular approaches their impact example highly specialized applications moved specialists primary care providers (e.g., pharmacogenetic pharmacogenomic routine medical practice). needs follow path established approach. To pharmacological bases existing gap by means omics will pave way discovery identification novel drug-targets/therapeutic protocols, laboratory tests diagnostic procedures (sex/gender-omics). scenario, aim present review simply resume state-of-the-art field, rather opportunity gain insights into medicine, spanning up social psychological stances. description critical discussion some key selected multidisciplinary topics considered paradigmatic differences inequalities allow draft design strategies useful fill move forward.

Язык: Английский

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Near-infrared absorbing Ru(ii) complexes act as immunoprotective photodynamic therapy (PDT) agents against aggressive melanoma

Chemical Science, Год журнала: 2020, Номер 11(43), С. 11740 - 11762

Опубликована: Янв. 1, 2020

Ru(ii) photosensitizers (PSs) destroy aggressive melanoma cells, triggering an immune response that leads to protection against tumor challenge and mouse survival.

Язык: Английский

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