Sex dimorphism and cancer immunotherapy: May pregnancy solve the puzzle?

Venanzi, Francesco Maria; Bini, Marta; Nuccio, Antonio; De Toma, Alessandro; Lambertini, Matteo; Ogliari, Francesca Rita; Oresti, Sara; Viganò, Maria Grazia; Brioschi, Elena; Polignano, Maggie; Naldini, Matteo Maria; Riva, Silvia; Ferrara, Michele; Fogale, Nicola; Damiano, Giuseppe; Russo, Vincenzo; Reni, Michele; Veronesi, Giulia; Foggetti, Giorgia; Conforti, Fabio; Bulotta, Alessandra; Ferrara, Roberto

doi:10.1016/j.ctrv.2023.102648

Cited by 3 publications

(1 citation statement)

References 107 publications

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“…There have been reported promotive effects of pregnancy on regulatory immunity [139], and similar effects may persist long after pregnancy [140]. Fetalmaternal microchimerism and immune memory for shared cancer trophoblast antigens may be potential mechanisms of the effect [141]. In addition, we speculate that differences in the microbial environment between males and females may be an influential factor to be considered [142,143], although more adequate evidence is still needed to demonstrate the relationship between the two.…”

Section: Discussionmentioning

confidence: 79%

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Zhong,

Sun,

Zeng

et al. 2024

Cancers

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Background: Sex is an important factor influencing the immune system, and the distribution of tumors, including their types and subtypes, is characterized by sexual dichotomy. The aim of this study was to investigate whether there is an association between sex and the treatment effect of immune checkpoint inhibitors (ICI). Methods: Four bibliographic databases were searched. Studies of randomized controlled trials (RCTs) assessing the efficacy of ICI were identified and used, and the primary endpoint was the difference in efficacy of ICI between males and females, presented as overall survival (OS), progression-free survival (PFS) and recurrence-free survival (RFS). The study calculated the pooled HRs and 95% CIs for OS, PFS and RFS for males and females using a random effects model or a fixed effects model, and thereby assessed the effect of sex on the efficacy of ICI treatment. This study is registered with PROSPERO (CRD42022370939). Results: A total of 103 articles, including a total of 63,755 patients with cancer, were retrieved from the bibliographic database, of which approximately 70% were males. In studies with OS as the outcome, the combined hazard ratio (HR) was 0.77 (95% CI 0.74–0.79) for male patients treated with ICI and 0.81 (95% CI 0.78–0.85) for female patients compared to controls, respectively. The difference in efficacy between males and females was significant. Conclusions: ICI therapy, under suitable conditions for its use, has a positive impact on survival in various types of tumors, and male patients benefit more than females. It may be necessary to develop different tumor immunotherapy strategies for patients of different sexes.

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Section: Discussionmentioning

confidence: 79%

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Zhong,

Sun,

Zeng

et al. 2024

Cancers

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Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy

Corti,

Binboğa Kurt,

Koca

et al. 2025

Cancer Treatment Reviews

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Sex-specific difference for melanoma from immunotherapy advancement

Li,

Dong,

et al. 2024

Front. Oncol.

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BackgroundThe evaluation of melanoma incidence and mortality trends based on population characteristics, with a particular focus on sex differences, is of utmost importance.MethodsThe gender-stratified analysis of melanoma mortality across various calendar years was conducted. Utilizing the Joinpoint software, we detected alterations in the incidence rates and delineated the mortality trends.ResultsMelanoma’s incidence-based mortality exhibited a rising trajectory between 2005 and 2010, characterized by an annual percent change (APC) of 2.95%. However, there was a significant decrease in mortality from 2015 to 2019, with an APC of -4.39%. Notably, the mortality among men decreased by about 5.84% between 2015 and 2019, while there was no significant downward trend in the mortality rate among women. Subsequent analysis revealed no statistically significant variation in the 2-year survival rate of female patients aged 45-54 years among different age groups (Z=-0.775, p >0.1).ConclusionsBetween 2015 and 2019, against the backdrop of stable melanoma incidence rates in the United States, there was a significant decline in mortality. Our analysis suggests that the utilization of immunotherapy may account for the observed reduction in mortality, with particularly notable benefits for male patients. However, female patients, especially younger women, did not derive significant advantages.

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Sex dimorphism and cancer immunotherapy: May pregnancy solve the puzzle?

Cited by 3 publications

References 107 publications

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

The Effect of Sex on the Therapeutic Efficiency of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis Based on Randomized Controlled Trials

Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy

Sex-specific difference for melanoma from immunotherapy advancement

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