Cetintas Vildan B, Batada Nizar N
Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey.
Centre for Genomic and Experimental Medicine, MRC Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, UK.
J Transl Med. 2020 Jan 30;18(1):45. doi: 10.1186/s12967-020-02219-w.
The PTEN tumor suppressor is the second most commonly inactivated gene across cancer types. While it's role in PI3K/AKT and DNA damage pathways are clear, increasing evidences suggest that PTEN may also promote anti-tumor immunity. PTEN-deficient tumors are characterized by (i) reduced levels of cytotoxic T cells, helper T cells and NK cells, (ii) elevated pro-oncogenic inflammatory cytokines like CCL2 and (iii) increased levels of immunosuppressive cells such as MDSCs and Tregs. An intriguing possibility is that link between PTEN and anti-tumor immunity is mediated by the interferon signaling pathway. In this review, we summarize the evidences for the mechanistic link between PTEN deficiency and immunosuppressive tumor microenvironment and the interferon signaling pathway. We further discuss how the link between these pathways can be exploited for development of personalized immunotherapy for patients with PTEN deficient tumors.
PTEN肿瘤抑制基因是各类癌症中第二常见的失活基因。虽然其在PI3K/AKT和DNA损伤通路中的作用已很明确，但越来越多的证据表明，PTEN可能也会促进抗肿瘤免疫。PTEN缺陷型肿瘤的特征包括：（i）细胞毒性T细胞、辅助性T细胞和自然杀伤细胞水平降低；（ii）促癌炎症细胞因子如CCL2水平升高；（iii）免疫抑制细胞如骨髓来源的抑制细胞（MDSCs）和调节性T细胞（Tregs）水平增加。一个有趣的可能性是，PTEN与抗肿瘤免疫之间的联系是由干扰素信号通路介导的。在本综述中，我们总结了PTEN缺陷与免疫抑制性肿瘤微环境及干扰素信号通路之间机制联系的证据。我们还进一步讨论了如何利用这些通路之间的联系，为PTEN缺陷型肿瘤患者开发个性化免疫疗法。
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