Immune Checkpoint Inhibition for Triple-Negative Breast Cancer: Current Landscape and Future Perspectives.
Immune Checkpoint Inhibition for Triple-Negative Breast Cancer: Current Landscape and Future Perspectives.
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三阴性乳腺癌的免疫检查点抑制：现状和未来前景
DOI：
10.3389/fonc.2021.648139
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发表时间：
2021
影响因子：
4.7
通讯作者：
Deng X
中科院分区：
文献类型：
--
作者：
Yi H;Li Y;Tan Y;Fu S;Tang F;Deng X
三阴性乳腺癌（TNBC）的特征在于缺乏临床显著水平的雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER 2）。由于侵袭性和对化疗药物耐药性的出现，TNBC患者的预后比其他亚型的乳腺癌更差。目前，使用检查点封锁的免疫疗法已被证明可以在多种癌症患者中产生前所未有的持久反应率。尽管乳腺肿瘤通常不是高度免疫原性的，但TNBC具有更高水平的淋巴细胞浸润，这表明TNBC患者可能对免疫疗法更敏感。免疫检查点分子的鉴定/表征，即，程序性细胞死亡蛋白1（PD 1）、程序性细胞死亡配体1（PDL 1）和细胞毒性T淋巴细胞相关抗原4（CTLA 4）代表了癌症免疫治疗领域的重大进展。这些分子的功能是抑制T细胞受体（TCR）活化下游的信号，导致细胞毒性T淋巴细胞（CTL）的消除和抗肿瘤免疫的抑制。对于TNBC，几十年来在临床管理方面没有取得实质性进展，免疫检查点抑制提供了持久反应和潜在长期益处的机会。在临床研究中，免疫检查点抑制在早期和晚期TNBC患者中产生了有希望的结果。本文综述了TNBC免疫检查点抑制的最新进展，重点是针对PD 1/PDL 1和CTLA 4通路的人源化抗体。
Triple-negative breast cancer (TNBC) is characterized by the lack of clinically significant levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Owing to the aggressive nature and the emergence of resistance to chemotherapeutic drugs, patients with TNBC have a worse prognosis than other subtypes of breast cancer. Currently, immunotherapy using checkpoint blockade has been shown to produce unprecedented rates of long-lasting responses in patients with a variety of cancers. Although breast tumors, in general, are not highly immunogenic, TNBC has a higher level of lymphocyte infiltration, suggesting that TNBC patients may be more responsive to immunotherapy. The identification/characterization of immune checkpoint molecules, i.e., programmed cell death protein 1 (PD1), programmed cell death ligand 1 (PDL1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), represents a major advancement in the field of cancer immunotherapy. These molecules function to suppress signals downstream of T cell receptor (TCR) activation, leading to elimination of cytotoxic T lymphocytes (CTLs) and suppression of anti-tumor immunity. For TNBC, which has not seen substantial advances in clinical management for decades, immune checkpoint inhibition offers the opportunity of durable response and potential long-term benefit. In clinical investigations, immune checkpoint inhibition has yielded promising results in patients with early-stage as well as advanced TNBC. This review summarizes the recent development of immune checkpoint inhibition in TNBC, focusing on humanized antibodies targeting the PD1/PDL1 and the CTLA4 pathways.
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