Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Street, 90-363 Lodz, Poland.
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, 112 Sienkiewicza Street, 90-363 Lodz, Poland.
Immunobiology. 2014 Feb;219(2):158-65. doi: 10.1016/j.imbio.2013.09.003. Epub 2013 Sep 8.
The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell-cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.
免疫系统是对抗恶性转化的重要第一道防线。然而，癌症介导的免疫抑制使宿主免疫监视机制失活。癌细胞通过与白细胞的直接细胞-细胞相互作用以及通过可溶性因子，关闭抗肿瘤免疫，为癌症的不受阻碍的生长建立一个免疫抑制环境。乳腺癌肿瘤中免疫抑制微环境的组成尚未得到很好的记录。为了解决这个问题，在手术后对 33 名乳腺癌患者的肿瘤标本中分析了选定的免疫抑制因子。在新鲜肿瘤样本中定量分析了选定基因的 mRNA 表达。通过流式细胞术对肿瘤浸润的白细胞进行表征，以鉴定调节性 T 细胞、髓系来源的抑制细胞和 2 型巨噬细胞。统计分析揭示了研究参数与临床特征之间的几个有趣相关性。总体而言，在所有乳腺癌样本中发现免疫抑制环境组成的高度异质性，这增加了该疾病的复杂性。还研究了缺氧诱导因子 (HIFs) 对免疫微环境的影响。HIF 水平与激素受体状态和几种免疫抑制分子的表达相关。靶向 HIFs 不仅可能使乳腺癌肿瘤对放射和化疗敏感，而且可能干扰癌症免疫抑制。
