Embracing cancer complexity: Hallmarks of systemic disease

Cell, Год журнала: 2024, Номер 187(7), С. 1589 - 1616

Опубликована: Март 1, 2024

Язык: Английский

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Sex disparities in the incidence of 21 cancer types: Quantification of the contribution of risk factors

Cancer, Год журнала: 2022, Номер 128(19), С. 3531 - 3540

Опубликована: Авг. 8, 2022

Background Cancer incidence is higher in men than women at most shared anatomic sites for currently unknown reasons. The authors quantified the extent to which behaviors (smoking and alcohol use), anthropometrics (body mass index height), lifestyles (physical activity, diet, medications), medical history collectively explain male predominance of risk 21 cancer sites. Methods Prospective cohort analyses ( n = 171,274 122,826 female participants; age range, 50–71 years) National Institutes Health‐AARP Diet Health Study (1995–2011). Cancer‐specific Cox regression models were used estimate male‐to‐female hazard ratios (HRs). degree factors explained observed male–female disparity was using Peters–Belson method. Results There 26,693 incident cancers (17,951 8742 women). Incidence significantly lower only thyroid gallbladder cancers. At other sites, risks (adjusted HR 1.3–10.8), with strongest increases bladder (HR, 3.33; 95% confidence interval [CI], 2.93–3.79), gastric cardia 3.49; CI, 2.26–5.37), larynx 3.53; 2.46–5.06), esophageal adenocarcinoma 10.80; 7.33–15.90). Risk a statistically significant (nonzero) proportion excess liver, biliary tract, bladder, skin, colon, rectum, lung. However, modest by (ranging from 50% lung 11% adenocarcinoma). Conclusions Men have Such largely unexplained factors, underscoring role sex‐related biologic factors.

Язык: Английский

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Androgen receptor-mediated CD8+ T cell stemness programs drive sex differences in antitumor immunity

Immunity, Год журнала: 2022, Номер 55(7), С. 1268 - 1283.e9

Опубликована: Июнь 13, 2022

Язык: Английский

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The spectrum of sex differences in cancer

Trends in cancer, Год журнала: 2022, Номер 8(4), С. 303 - 315

Опубликована: Фев. 18, 2022

HighlightsSex differences in cancer incidence and survival are the norm evident across types, around globe, all genetic ancestries, age groups.Increasingly, sex cancer-relevant cellular systems biology being described.Sex mutational burden, DNA repair, epigenetics, metabolism, tumor suppressor activity, cell cycle regulation, immunity reported.AbstractSex have been evolutionarily selected to optimize reproductive success species with little (sperm) big (ova) gamete producers. They from time of fertilization accrue throughout development through genetic, epigenetic, circulating hormone-dependent mechanisms. Among other effects, they significantly impact on chromatin organization, immunity, longevity, risk survival. Sex should be expected accounted for basic, translational, clinical oncology research.

Язык: Английский

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Histone demethylase KDM5D upregulation drives sex differences in colon cancer

Nature, Год журнала: 2023, Номер 619(7970), С. 632 - 639

Опубликована: Июнь 21, 2023

Язык: Английский

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Mechanisms and consequences of sex differences in immune responses

Nature Reviews Nephrology, Год журнала: 2023, Номер 20(1), С. 37 - 55

Опубликована: Ноя. 22, 2023

Язык: Английский

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Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma

Cancer Discovery, Год журнала: 2023, Номер 13(9), С. 2090 - 2105

Опубликована: Июнь 28, 2023

Abstract Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, emerging evidence suggests that these extend to genetic/epigenetic cellular differences, including immune responses. However, the mechanisms driving immunologic sex not fully understood. Here, we demonstrate T cells play a critical role GBM differences. Male mice exhibited accelerated tumor growth, with decreased frequency increased exhaustion of CD8+ tumor. Furthermore, higher progenitor exhausted was found males, improved responsiveness anti–PD-1 treatment. Moreover, T-cell observed male patients. Bone marrow chimera adoptive transfer models indicated cell–mediated control predominantly regulated cell-intrinsic manner, partially mediated by X chromosome inactivation escape gene Kdm6a. These findings sex-biased predetermined behavior is for inducing progression immunotherapy response. Significance: Immunotherapies patients have been unsuccessful due variety factors, highly immunosuppressive microenvironment GBM. This study demonstrates behaviors intrinsically regulated, further suggesting sex-specific approaches can be leveraged potentially improve therapeutic efficacy See related commentary Alspach, p. 1966. article featured Selected Articles from Issue, 1949

Язык: Английский

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Androgen Signaling Contributes to Sex Differences in Cancer by Inhibiting NF-κB Activation in T Cells and Suppressing Antitumor Immunity

Cancer Research, Год журнала: 2023, Номер 83(6), С. 906 - 921

Опубликована: Янв. 12, 2023

Sex is known to be an important factor in the incidence, progression, and outcome of cancer. A better understanding underlying mechanisms could help improve cancer prevention treatment. Here, we demonstrated a crucial role antitumor immunity sex differences Consistent with observations human cancers, male mice showed accelerated tumor progression compared females, but these were not observed immunodeficient mice. Androgen signaling suppressed T-cell against males. Mechanistically, androgen-activated androgen receptor upregulated expression USP18, which inhibited TAK1 phosphorylation subsequent activation NF-κB T cells. Reduction testosterone synthesis by surgical castration or using small-molecular inhibitor abiraterone significantly enhanced activity cells improved efficacy anti-PD-1 immunotherapy. Together, this study revealed novel mechanism contributing These results indicate that inhibition promising approach immunotherapy males.Androgen induces immunosuppression blocking through upregulation USP18 activity, providing targetable axis

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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A life-course approach to tackling noncommunicable diseases in women

Nature Medicine, Год журнала: 2024, Номер 30(1), С. 51 - 60

Опубликована: Янв. 1, 2024

Язык: Английский

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