Department of Breast and Thyroid Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650011, P.R. China.
Department of Emergency Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230000, P.R. China.
Mol Med Rep. 2018 Nov;18(5):4247-4258. doi: 10.3892/mmr.2018.9460. Epub 2018 Sep 5.
Tumor-infiltrating lymphocytes are associated with the response to neoadjuvent chemotherapy and prognosis in breast cancer. However, the distribution, interaction and prognostic value of tumor‑infiltrating T cells, the main component of the tumor microenvironment, have seldom been reported. In the present study, surgical specimens of 72 breast cancer patients were analyzed. Tumor‑infiltrating T cell subsets [cluster of differentiation (CD)4+T, CD8+T and regulatory T cells] and expression of their cytokines [interferon‑γ, interleukin (IL)‑4, and IL‑17] were evaluated by flow cytometry. These parameters together with The Cancer Genome Atlas database were used to demonstrate the distribution, interaction and prognostic value of tumor‑infiltrating T cells in breast cancer. Tumor‑infiltrating lymphocytes were closely associated with histological grade (P=0.03), estrogen receptor status (P=0.006), human epidermal growth factor receptor 2 status (P=0.047) and molecular subtype in breast cancer (P=0.012). The gene expression of CD4, CD8A and forkhead box protein P3 in the tumor was increased compared with healthy breast tissue, and was positively associated with the prognosis of breast cancer patients. HER2+ and triple‑negative breast cancer exhibited a significantly increased percentage of CD4+T cells (P=0.01) and regulatory T cells (P=0.035), and a decreased percentage of CD8+T cells (P=0.006) compared with the luminal subtype. Furthermore, the regulatory T cell number was positively correlated with CD8+T cell number in tumors (R=0.7, P=1.5x10‑162) and significantly inhibited the cytokine secretion of T cells. These results reveal the distribution and interaction of tumor‑infiltrating T cell subsets, and indicate that CD8+T cells and regulatory T cells may be used as reliable predictors of prognosis in breast cancer.
肿瘤浸润淋巴细胞与乳腺癌新辅助化疗反应和预后相关。然而,肿瘤微环境的主要组成部分——肿瘤浸润 T 细胞的分布、相互作用及其预后价值很少被报道。在本研究中,分析了 72 例乳腺癌患者的手术标本。通过流式细胞术评估肿瘤浸润 T 细胞亚群(CD4+T、CD8+T 和调节性 T 细胞)及其细胞因子(干扰素-γ、白细胞介素(IL)-4 和 IL-17)的表达。这些参数以及癌症基因组图谱数据库用于证明乳腺癌中肿瘤浸润 T 细胞的分布、相互作用及其预后价值。肿瘤浸润淋巴细胞与组织学分级(P=0.03)、雌激素受体状态(P=0.006)、人类表皮生长因子受体 2 状态(P=0.047)和乳腺癌分子亚型(P=0.012)密切相关。与健康乳腺组织相比,肿瘤中 CD4、CD8A 和叉头框蛋白 P3 的基因表达增加,与乳腺癌患者的预后呈正相关。与管腔亚型相比,HER2+和三阴性乳腺癌的 CD4+T 细胞(P=0.01)和调节性 T 细胞(P=0.035)的比例显著增加,CD8+T 细胞的比例显著降低(P=0.006)。此外,调节性 T 细胞的数量与肿瘤中 CD8+T 细胞的数量呈正相关(R=0.7,P=1.5x10-162),并显著抑制 T 细胞的细胞因子分泌。这些结果揭示了肿瘤浸润 T 细胞亚群的分布和相互作用,并表明 CD8+T 细胞和调节性 T 细胞可能作为乳腺癌预后的可靠预测指标。