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

Q2 Agricultural and Biological Sciences Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI:10.1016/j.crphar.2022.100146

Giulia Mazzaschi , Federico Quaini , Sebastiano Buti

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引用次数: 1

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.

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探索肿瘤对免疫检查点抑制剂的性二态性反应的遗传和免疫基础:叙述回顾

引言尽管性别作为免疫景观的关键生物变量具有无可争议的相关性，但我们对癌症患者性偏倚免疫反应的基本机制的理解仍然有限，从而制约了患者的治疗结果。这种阻碍推迟了解读癌症异质性及其免疫监测的实际尝试，进一步偏离了在当前免疫治疗驱动的情况下预测生物标志物的实现。正文：本综述简要报道了免疫检查点抑制剂（ICIs）反应中潜在性别差异的遗传、染色体、激素和免疫特征。除了概述对ICI药物动力学/动力学的可靠数据的需求外，我们的调查可能会对ICI疗效的性别决定因素提供新的见解，并提出值得前瞻性研究的未发现途径。结论根据一个共同的观点，我们建议在评估癌症患者对ICI的临床反应时，将性别广泛纳入协变量。

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