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Review
. 2022 Dec 7:4:100146.
doi: 10.1016/j.crphar.2022.100146. eCollection 2023.

Exploring genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review

Giulia Mazzaschi  1   2 , Federico Quaini  2 , Sebastiano Buti  1   2
Affiliations
Review

Exploring genetic and immune underpinnings of the sexual dimorphism in tumor response to immune checkpoints inhibitors: A narrative review

Giulia Mazzaschi et al. Curr Res Pharmacol Drug Discov. .

Abstract

Introduction: In spite of the undisputed relevance of sex as critical biologic variable of the immune landscape, still limited is our understanding of the basic mechanisms implicated in sex-biased immune response thereby conditioning the therapeutic outcome in cancer patients. This hindrance delays the actual attempts to decipher the heterogeneity of cancer and its immune surveillance, further digressing the achievement of predictive biomarkers in the current immunotherapy-driven scenario. Body: The present review concisely reports on genetic, chromosomal, hormonal, and immune features underlying sex-differences in the response to immune checkpoint inhibitors (ICIs). In addition to outline the need of robust data on ICI pharmaco-kinetics/dynamics, our survey might provide new insights on sex determinants of ICI efficacy and suggests uncovered pathways that warrant prospective investigations.

Conclusion: According to a sharable view, we propose to widely include sex among the co-variates when assessing the clinical response to ICI in cancer patients.

Keywords: Cancer patients; Genetic background; Immune checkpoint inhibitors; Immune response; Sex; Sex differences.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

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Graphical abstract
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