乳腺癌发病占女性恶性肿瘤的首位。三阴性乳腺癌（TNBC）易转移、预后差、缺乏有效的治疗靶点。我们前期研究发现不同类型乳腺癌微环境中肿瘤浸润淋巴细胞（TILs）的分布和功能状态不同；保持基因稳定性的关键性激酶ATM与TNBC肿瘤间质内TILs、淋巴结转移及放化疗耐药密切相关。结合文献我们提出“ATM可能通过调节肿瘤微环境的TILs，影响TNBC的生物学行为”的假说，需对其研究验证并对二者间的相互作用进行解析。本次申请立项研究，我们将以TNBC和非TNBC乳腺癌为对象，以ATM和TILs为核心，通过模拟“肿瘤微环境”，研究ATM不同表达和活化状态下，TILs和癌细胞中NKG2D、DNAM-1及其配体等的表达，动态观察TILs的免疫功能变化；并结合临床病理学特征，解析不同类型乳腺癌微环境中，ATM与TILs的相互调节和作用机制。为乳腺癌的精准诊治和研究提供依据。

The incidence of breast cancer accounts for the first place in female malignant tumor. Triple negative breast cancer (TNBC) is high metastasis, poor prognosis and lack of effective therapeutic targets. Our previous study found that the distribution and functional status of tumor infiltrating lymphocytes (TILs) were different in the microenvironment of different types of breast cancer. We also found that ATM - key kinase maintaining genome stability, is closely related to TILs, lymph node metastasis and drug resistance of radiotherapy and chemotherapy in TNBC. On the basis of these studies and combined with the literature, we propose research hypotheses that ATM may affect the biological behavior of TNBC by regulating TILs in the microenvironment. In this study, we will analyze the interaction and molecular mechanism between ATM and TILs in the microenvironment of different types of breast cancer (TNBC and non-TNBC). Moreover, "tumor microenvironment" will be simulated to study the expression of NKG2D, DNAM-1 and their ligands in TILs and cancer cells, and changes of immune function in TILs under different expression and activation of ATM. And we will analyze the interaction and mechanism between ATM and TILs in the microenvironment of different types of breast cancer by combined with clinical pathological features. Therefore, we will try to provide research basis for accurate diagnosis and treatment of breast cancer.