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免疫检查点抑制剂治疗三阴性乳腺癌:从免疫机制到临床证据。

Immune checkpoint inhibitors for triple-negative breast cancer: From immunological mechanisms to clinical evidence.

机构信息

School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Sheffield, UK.

出版信息

Int Immunopharmacol. 2021 Sep;98:107876. doi: 10.1016/j.intimp.2021.107876. Epub 2021 Jun 17.


DOI:10.1016/j.intimp.2021.107876
PMID:34146865
Abstract

Breast cancer is the most common cancer type in women worldwide. Triple-negative breast cancer (TNBC), which is characterized by the absence of estrogen receptor/progesterone receptor (ER/PR) and human epidermal growth factor receptor 2 (Her2) expressions, has a poorer prognosis compared with non-TNBC breast tumors. Until recently systemic treatment for TNBC was confined to chemotherapy owing to the lack of actionable targets. Immune checkpoint molecules are expressed on malignant cells or tumor-infiltrating immune cells and can inhibit anti-cancer immune responses. Immune checkpoint inhibitors (ICI), including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-programmed cell death protein 1 (PD-1), and anti-programmed cell death 1 ligand 1 (PD-L1), induce immune responses in different types of neoplasms. They have recently gained attention for their possible role in TNBC treatment. Several clinical trials have been conducted on the role of immune checkpoint blockade in different settings for TNBC treatment. Available evidence justifies the application of ICI and chemotherapy combination in the management of metastatic TNBC and early-stage TNBC in neoadjuvant setting. This study aims to provide information on the mechanisms of action of ICIs, review the efficacy results of clinical trials using ICIs for TNBC treatment, and assess the side effects of such drugs.

摘要

乳腺癌是全球女性最常见的癌症类型。三阴性乳腺癌(TNBC)的特点是缺乏雌激素受体/孕激素受体(ER/PR)和人表皮生长因子受体 2(Her2)的表达,与非 TNBC 乳腺肿瘤相比,预后更差。由于缺乏可靶向的靶点,直到最近,TNBC 的系统治疗仅限于化疗。免疫检查点分子在恶性细胞或肿瘤浸润免疫细胞上表达,可抑制抗肿瘤免疫反应。免疫检查点抑制剂(ICI),包括抗细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)、抗程序性细胞死亡蛋白 1(PD-1)和抗程序性细胞死亡配体 1(PD-L1),在不同类型的肿瘤中诱导免疫反应。它们最近因其在 TNBC 治疗中的可能作用而受到关注。已经进行了几项关于免疫检查点阻断在不同 TNBC 治疗环境中的作用的临床试验。现有证据证明了 ICI 和化疗联合应用于转移性 TNBC 和新辅助治疗中早期 TNBC 的管理。本研究旨在提供关于 ICI 作用机制的信息,回顾使用 ICI 治疗 TNBC 的临床试验的疗效结果,并评估这些药物的副作用。

相似文献

[1]
Immune checkpoint inhibitors for triple-negative breast cancer: From immunological mechanisms to clinical evidence.

Int Immunopharmacol. 2021-9

[2]
Determining Factors in the Therapeutic Success of Checkpoint Immunotherapies against PD-L1 in Breast Cancer: A Focus on Epithelial-Mesenchymal Transition Activation.

J Immunol Res. 2021

[3]
Triple‑negative breast cancer therapy: Current and future perspectives (Review).

Int J Oncol. 2020-12

[4]
The evolving role of immune checkpoint inhibitors in the treatment of triple-negative breast cancer.

Clin Adv Hematol Oncol. 2021-5

[5]
Eganelisib combined with immune checkpoint inhibitor therapy and chemotherapy in frontline metastatic triple-negative breast cancer triggers macrophage reprogramming, immune activation and extracellular matrix reorganization in the tumor microenvironment.

J Immunother Cancer. 2024-8-30

[6]
The anti-cancer immune response in breast cancer: current and emerging biomarkers and treatments.

Trends Cancer. 2024-6

[7]
Pembrolizumab and atezolizumab in triple-negative breast cancer.

Cancer Immunol Immunother. 2021-3

[8]
Biomarkers of Immune Checkpoint Blockade Response in Triple-Negative Breast Cancer.

Curr Treat Options Oncol. 2021-3-20

[9]
Immune checkpoint inhibitors plus neoadjuvant chemotherapy in early triple-negative breast cancer: a systematic review and meta-analysis.

BMC Cancer. 2021-11-23

[10]
PD‑L1/PD‑1 blockade in breast cancer: The immunotherapy era (Review).

Oncol Rep. 2021-1

引用本文的文献

[1]
Short- and long-term efficacy of olaparib combined with chemotherapy in advanced triple-negative breast cancer.

Am J Cancer Res. 2025-7-15

[2]
Radiation-Based Multi-Modal Therapy Combining with Immunotherapy to Develop a Vaccine-Like Effective Treatment for Triple-Negative Breast Cancer.

Breast Cancer (Dove Med Press). 2025-6-10

[3]
Immunohistochemical Expression of PD-L1 and CTLA-4 in Triple Negative Breast Cancer and Their Prognostic Associations.

Asian Pac J Cancer Prev. 2025-1-1

[4]
Low expression of TOX predicts poor prognosis of patients with breast cancer in the real world: A retrospective study.

Heliyon. 2024-12-12

[5]
Current applications of tumor local ablation (TLA) combined with immune checkpoint inhibitors in breast cancer treatment.

Cancer Drug Resist. 2024-9-13

[6]
Efficacy and safety of first-line treatment for metastatic triple-negative breast cancer: A network meta-analysis.

Cancer Pathog Ther. 2023-6-13

[7]
Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response.

Explor Target Antitumor Ther. 2024

[8]
Addition of immune checkpoint inhibitors to chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: A systematic review and meta-analysis.

Cancer Med. 2023-12

[9]
The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.

Front Immunol. 2023

[10]
PDLIM2 is highly expressed in Breast Cancer tumour-associated macrophages and is required for M2 macrophage polarization.

Front Oncol. 2022-11-30

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