Eissing Marc, Ripken Lise, Schreibelt Gerty, Westdorp Harm, Ligtenberg Marjolijn, Netea-Maier Romana, Netea Mihai G, de Vries I Jolanda M, Hoogerbrugge Nicoline
Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Geert Grooteplein Zuid 28, 6525, GA, Nijmegen, The Netherlands.
Department of Human Genetics, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.
Transl Oncol. 2019 Feb;12(2):361-367. doi: 10.1016/j.tranon.2018.11.003. Epub 2018 Nov 30.
Carriers of a pathogenic germline mutations in the PTEN gene, a well-known tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, e.g. breast, thyroid, endometrial and colon cancer. This is called PTEN Hamartomous Tumor Syndrome (PHTS). PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. The effects of PTEN on the immune system have been studied in murine knockout models demonstrating that loss of PTEN function leads to dysregulation of the immune response. This results in susceptibility to autoimmunity, impaired B cell class switching with subsequent hypogammaglobulinemia. Additionally, a decreased ability of dendritic cells to prime CD8 T cells was observed, leading to impaired tumor eradication. Immune dysfunction in PHTS patients has not yet been extensively studied but might be a manageable contributing factor to the increased cancer risk in PHTS.
PTEN基因是一种著名的肿瘤抑制基因，携带该基因致病性种系突变的个体患多种良性和恶性肿瘤的风险增加，如乳腺癌、甲状腺癌、子宫内膜癌和结肠癌。这被称为PTEN错构瘤综合征（PHTS）。PHTS患者出现免疫调节异常（如自身免疫和免疫缺陷）的风险也可能增加。在小鼠基因敲除模型中对PTEN对免疫系统的影响进行了研究，结果表明PTEN功能丧失会导致免疫反应失调。这会导致自身免疫易感性、B细胞类别转换受损并随后出现低丙种球蛋白血症。此外，还观察到树突状细胞激活CD8 T细胞的能力下降，导致肿瘤清除受损。PHTS患者的免疫功能障碍尚未得到广泛研究，但可能是导致PHTS患者癌症风险增加的一个可控因素。
