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癌症和免疫疗法疗效的性别差异:雄激素受体的作用。

Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor.

机构信息

Duke-NUS Medical School, Singapore, Singapore.

Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore.

出版信息

Front Immunol. 2024 May 28;15:1416941. doi: 10.3389/fimmu.2024.1416941. eCollection 2024.


DOI:10.3389/fimmu.2024.1416941
PMID:38863718
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11165033/
Abstract

Across the wide range of clinical conditions, there exists a sex imbalance where biological females are more prone to autoimmune diseases and males to some cancers. These discrepancies are the combinatory consequence of lifestyle and environmental factors such as smoking, alcohol consumption, obesity, and oncogenic viruses, as well as other intrinsic biological traits including sex chromosomes and sex hormones. While the emergence of immuno-oncology (I/O) has revolutionised cancer care, the efficacy across multiple cancers may be limited because of a complex, dynamic interplay between the tumour and its microenvironment (TME). Indeed, sex and gender can also influence the varying effectiveness of I/O. Androgen receptor (AR) plays an important role in tumorigenesis and in shaping the TME. Here, we lay out the epidemiological context of sex disparity in cancer and then review the current literature on how AR signalling contributes to such observation via altered tumour development and immunology. We offer insights into AR-mediated immunosuppressive mechanisms, with the hope of translating preclinical and clinical evidence in gender oncology into improved outcomes in personalised, I/O-based cancer care.

摘要

在广泛的临床病症中,存在一种性别不平衡现象,即女性更容易患自身免疫性疾病,而男性更容易患某些癌症。这些差异是生活方式和环境因素(如吸烟、饮酒、肥胖和致癌病毒)以及其他内在生物学特征(如性染色体和性激素)的综合结果。虽然免疫肿瘤学(I/O)的出现已经彻底改变了癌症治疗,但由于肿瘤及其微环境(TME)之间复杂的动态相互作用,其在多种癌症中的疗效可能会受到限制。事实上,性别也会影响 I/O 的不同疗效。雄激素受体(AR)在肿瘤发生和塑造 TME 中发挥着重要作用。在这里,我们阐述了癌症中性别差异的流行病学背景,然后回顾了目前关于 AR 信号如何通过改变肿瘤发生和免疫学来导致这种观察结果的文献。我们深入探讨了 AR 介导的免疫抑制机制,希望将性别肿瘤学中的临床前和临床证据转化为基于个性化 I/O 的癌症治疗中改善的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/fbf7d137d620/fimmu-15-1416941-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/9563f02eab2b/fimmu-15-1416941-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/a9a6b65fd41e/fimmu-15-1416941-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/c7cd1bf64cab/fimmu-15-1416941-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/fbf7d137d620/fimmu-15-1416941-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/9563f02eab2b/fimmu-15-1416941-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/a9a6b65fd41e/fimmu-15-1416941-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/c7cd1bf64cab/fimmu-15-1416941-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72db/11165033/fbf7d137d620/fimmu-15-1416941-g004.jpg

相似文献

[1]
Sex differences in cancer and immunotherapy outcomes: the role of androgen receptor.

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引用本文的文献

[1]
The Predictive Value of Red Cell Distribution Width in End-Stage Colorectal Cancers' 6-Month Palliative Chemotherapy Response-A Single Center's Experience.

J Pers Med. 2025-8-7

[2]
Dihydrotestosterone-androgen receptor signaling suppresses EBV-positive gastric cancer through DNA demethylation-mediated viral reactivation.

Gastric Cancer. 2025-6-12

[3]
Androgen receptor signalling in non-prostatic malignancies: challenges and opportunities.

Nat Rev Cancer. 2025-2

本文引用的文献

[1]
Gender oncology: recommendations and consensus of the Italian Association of Medical Oncology (AIOM).

ESMO Open. 2024-2

[2]
Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma.

NEJM Evid. 2022-8

[3]
ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation.

Nat Commun. 2024-2-3

[4]
A meta-analysis and real-world cohort study on the sex-related differences in efficacy and safety of immunotherapy for hepatocellular carcinoma.

JHEP Rep. 2023-12-12

[5]
Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study.

Lancet Oncol. 2024-1

[6]
Identification of a targetable JAK-STAT enriched androgen receptor and androgen receptor splice variant positive triple-negative breast cancer subtype.

Cell Rep. 2023-12-26

[7]
Androgen receptor inhibition suppresses anti-tumor neutrophil response against bone metastatic prostate cancer via regulation of TβRI expression.

Cancer Lett. 2023-11-28

[8]
Androgen receptor is a determinant of melanoma targeted drug resistance.

Nat Commun. 2023-10-14

[9]
The Burden of Lung Cancer in Women Compared With Men in the US.

JAMA Oncol. 2023-12-1

[10]
Estrogen receptor β affects hypoxia response in colorectal cancer cells.

Biochim Biophys Acta Mol Basis Dis. 2024-1

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