表皮生长因子受体酪氨酸激酶抑制剂治疗前后表皮生长因子受体突变的非小细胞肺癌中的肿瘤免疫微环境：一篇叙述性综述
Tumor immune microenvironment in epidermal growth factor receptor-mutated non-small cell lung cancer before and after epidermal growth factor receptor tyrosine kinase inhibitor treatment: a narrative review.
作者信息
Liu Lihui, Wang Chao, Li Sini, Bai Hua, Wang Jie
机构信息
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Transl Lung Cancer Res. 2021 Sep;10(9):3823-3839. doi: 10.21037/tlcr-21-572.
OBJECTIVE
To review and summarize the characteristics of the tumor immune microenvironment (TIME) in EGFR-mutated non-small cell lung cancer (NSCLC) after EGFR-TKI treatment and its role in TKI resistance.
BACKGROUND
Lung cancer is one of the most commonly diagnosed cancer and the leading cause of death from cancer in both men and women around the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are considered a first-line treatment for EGFR-mutated NSCLC. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, with a median progression-free survival (PFS) of 9-14 months. As immunotherapy has developed, it has become apparent that interactions between the TIME and tumor cells also affect EGFR-TKI treatment. The TIME comprises a variety of components but previous studies of the TIME following EGFR-TKI therapy of NSCLC are inconsistent. Here, we reviewed the characteristics of the TIME in NSCLC after EGFR-TKI treatment and its role in TKI resistance.
METHODS
PubMed, Embase, and Web of Science were searched to July 1, 2021 with the following key words: "NSCLC", "EGFR", and "immunotherapy".
CONCLUSIONS
The TIME of EGFR-mutated NSCLC is different from that of non-mutated NSCLC, an explanation for EGFR-mutated NSCLC displaying a poor response to ICIs. The TIME of EGFR-mutated NSCLC also changes during treatment with EGFR-TKIs. The TIME in EGFR-TKI-resistant lung cancer can be summarized as follows: (I) compared with EGFR-TKI-sensitive tumors, EGFR-TKI-resistant tumors have a greater number of immunosuppressive cells and fewer immune-activated cells, while the tumor microenvironment is in an immunosuppressive state; (II) tumor cells and immunosuppressive cells secrete multiple negative immune regulatory factors, inhibit the recognition and presentation of tumor antigens and the antitumor effect of immune cells, resulting in immune escape; 3.EGFR-TKI-resistant tumors promote EMT. These three characteristics interact, resulting in a regulatory signaling network, which together leads to EGFR-TKI resistance.
目的
回顾并总结表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）在接受EGFR酪氨酸激酶抑制剂（TKI）治疗后的肿瘤免疫微环境（TIME）特征及其在TKI耐药中的作用。
背景
肺癌是全球最常被诊断出的癌症之一，也是男性和女性癌症死亡的主要原因。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）被认为是EGFR突变NSCLC的一线治疗方法。然而，几乎所有患者最终都会对EGFR-TKIs产生获得性耐药，中位无进展生存期（PFS）为9至14个月。随着免疫疗法的发展，很明显TIME与肿瘤细胞之间的相互作用也会影响EGFR-TKI治疗。TIME由多种成分组成，但先前关于NSCLC接受EGFR-TKI治疗后TIME的研究结果并不一致。在此，我们回顾了EGFR-TKI治疗后NSCLC中TIME的特征及其在TKI耐药中的作用。
方法
检索截至2021年7月1日的PubMed、Embase和Web of Science，关键词如下：“NSCLC”、“EGFR”和“免疫疗法”。
结论
EGFR突变的NSCLC的TIME与未突变的NSCLC不同，这解释了EGFR突变的NSCLC对免疫检查点抑制剂（ICIs）反应不佳的原因。EGFR突变的NSCLC的TIME在接受EGFR-TKIs治疗期间也会发生变化。EGFR-TKI耐药肺癌中的TIME可总结如下：（I）与EGFR-TKI敏感肿瘤相比，EGFR-TKI耐药肿瘤具有更多免疫抑制细胞和更少免疫激活细胞，而肿瘤微环境处于免疫抑制状态；（II）肿瘤细胞和免疫抑制细胞分泌多种负性免疫调节因子，抑制肿瘤抗原的识别与呈递以及免疫细胞的抗肿瘤作用，导致免疫逃逸；3.EGFR-TKI耐药肿瘤促进上皮-间质转化（EMT）。这三个特征相互作用，形成一个调节信号网络，共同导致EGFR-TKI耐药。
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