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当前对卵巢癌为何对免疫检查点抑制剂产生耐药性的认识。

Current Understanding on Why Ovarian Cancer Is Resistant to Immune Checkpoint Inhibitors.

机构信息

Independent Laboratory of Cancer Diagnostics and Immunology, Department of Oncological Gynaecology and Gynaecology, Faculty of Medicine, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.

Students' Scientific Association, Independent Laboratory of Cancer Diagnostics and Immunology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland.

出版信息

Int J Mol Sci. 2023 Jun 29;24(13):10859. doi: 10.3390/ijms241310859.


DOI:10.3390/ijms241310859
PMID:37446039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10341806/
Abstract

The standard treatment of ovarian cancer (OC) patients, including debulking surgery and first-line chemotherapy, is unsatisfactory because of recurrent episodes in the majority (~70%) of patients with advanced OC. Clinical trials have shown only a modest (10-15%) response of OC individuals to treatment based on immune checkpoint inhibitors (ICIs). The resistance of OC to therapy is caused by various factors, including OC heterogeneity, low density of tumor-infiltrating lymphocytes (TILs), non-cellular and cellular interactions in the tumor microenvironment (TME), as well as a network of microRNA regulating immune checkpoint pathways. Moreover, ICIs are the most efficient in tumors that are marked by high microsatellite instability and high tumor mutation burden, which is rare among OC patients. The great challenge in ICI implementation is connected with distinguishing hyper-, pseudo-, and real progression of the disease. The understanding of the immunological, molecular, and genetic mechanisms of OC resistance is crucial to selecting the group of OC individuals in whom personalized treatment would be beneficial. In this review, we summarize current knowledge about the selected factors inducing OC resistance and discuss the future directions of ICI-based immunotherapy development for OC patients.

摘要

卵巢癌 (OC) 患者的标准治疗方法,包括肿瘤细胞减灭术和一线化疗,由于大多数(约 70%)晚期 OC 患者的复发,效果并不令人满意。临床试验表明,基于免疫检查点抑制剂 (ICI) 的治疗对 OC 个体的反应仅适度(10-15%)。OC 对治疗的耐药性是由多种因素引起的,包括 OC 异质性、肿瘤浸润淋巴细胞 (TIL) 密度低、肿瘤微环境 (TME) 中的非细胞和细胞相互作用,以及调节免疫检查点途径的 microRNA 网络。此外,ICI 在高微卫星不稳定性和高肿瘤突变负担标记的肿瘤中最有效,而 OC 患者中这种情况很少见。ICI 实施的巨大挑战与区分疾病的高、假性和真正进展有关。了解 OC 耐药的免疫、分子和遗传机制对于选择将个性化治疗有益于 OC 个体的群体至关重要。在这篇综述中,我们总结了目前关于诱导 OC 耐药的选定因素的知识,并讨论了 OC 患者基于 ICI 的免疫治疗发展的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/7704a2b2582e/ijms-24-10859-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/7aa3134a64d1/ijms-24-10859-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/74b01cccfec4/ijms-24-10859-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/7704a2b2582e/ijms-24-10859-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/7aa3134a64d1/ijms-24-10859-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/74b01cccfec4/ijms-24-10859-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bb2/10341806/7704a2b2582e/ijms-24-10859-g003.jpg

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引用本文的文献

[1]
Role of Immunotherapy in Ovarian Cancer: Advances, Challenges, and Future Perspectives.

Cancer Treat Res. 2025

[2]
Immunotherapy for Platinum-Resistant Ovarian Cancer as a Glimmer of Hope.

Cells. 2025-6-29

[3]
Development of a prognostic immune cell-based model for ovarian cancer using multiplex immunofluorescence.

J Transl Med. 2025-6-19

[4]
Treatment of ovarian cancer: From the past to the new era (Review).

Oncol Lett. 2025-6-3

[5]
Functional heterogeneity and clinical implications of CD4+ T cell subtypes in high-grade serous ovarian carcinoma.

World J Clin Oncol. 2025-5-24

[6]
Study of the Role of the Tumor Microenvironment in Ovarian Cancer (MICO): A Prospective Monocentric Trial.

Cancer Rep (Hoboken). 2025-6

[7]
Multi-dimensional characterization of cellular states reveals clinically relevant immunological subtypes and therapeutic vulnerabilities in ovarian cancer.

J Transl Med. 2025-5-8

[8]
Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer.

J Immunother Cancer. 2025-3-13

[9]
Targeting TOP2A in Ovarian Cancer: Biological and Clinical Implications.

Curr Oncol. 2024-12-20

[10]
TIGIT CD4 regulatory T cells enhance PD-1 expression on CD8 T cells and promote tumor growth in a murine ovarian cancer model.

J Ovarian Res. 2024-12-20

本文引用的文献

[1]
Cancer-biomarkers associated with sex hormone receptors and recent therapeutic advancements: a comprehensive review.

Med Oncol. 2023-5-10

[2]
Advances in the application of immune checkpoint inhibitors in gynecological tumors.

Int Immunopharmacol. 2023-4

[3]
Early diagnosis of ovarian cancer based on methylation profiles in peripheral blood cell-free DNA: a systematic review.

Clin Epigenetics. 2023-2-14

[4]
Immune checkpoint inhibitor combinations-current and emerging strategies.

Br J Cancer. 2023-4

[5]
Application of Immune Checkpoint Inhibitors in Gynecological Cancers: What Do Gynecologists Need to Know before Using Immune Checkpoint Inhibitors?

Int J Mol Sci. 2023-1-4

[6]
Mirvetuximab Soravtansine: First Approval.

Drugs. 2023-2

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CD8 T cell exhaustion and cancer immunotherapy.

Cancer Lett. 2023-4-10

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The Dual Blockade of the TIGIT and PD-1/PD-L1 Pathway as a New Hope for Ovarian Cancer Patients.

Cancers (Basel). 2022-11-23

[9]
Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer.

Nat Commun. 2022-11-28

[10]
miRNAs in Regulation of Tumor Microenvironment, Chemotherapy Resistance, Immunotherapy Modulation and miRNA Therapeutics in Cancer.

Int J Mol Sci. 2022-11-10

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