癌症中的DNA损伤应答和炎症

2023-04-17 10:56

越来越多的临床前期和临床证据表明，DDR作为细胞保护有机体稳态的外源性程序的一部分，与正常、恶性细胞发放免疫调节信号密切相关。

SCI 16 April 2023

The DNA Damage Response and Inflammation in Cancer

（Cancer discovery IF：38.272）

Corresponding Author: Lorenzo Galluzzi, Weill Cornell Medical College, Stich Radiation Oncology, 525 East 68th Street, Box #169, New York, NY 10065. Phone: 646-962-2095; E-mail: deadoc80@gmail.com

ABSTRACT 摘要

Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting the demise of cells with unrepairable DNA lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR signaling can also favor tumor progression and resistance to therapy. Indeed, DDR signaling in cancer cells has been consistently linked to the inhibition of tumor-targeting immune responses. Here, we discuss the complex interactions between the DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy.

正常细胞的基因组稳定性对于避免肿瘤发生至关重要。因此，DNA损伤应答（DDR）的多个组分作为真正的肿瘤抑制蛋白，通过保持基因组稳定性，引起具有不可修复的DNA损伤的细胞死亡，并通过免疫监视进行细胞外源性肿瘤抑制。也就是说，DDR信号也可有利于肿瘤进展和抵抗治疗。事实上，癌细胞中的DDR信号一直与抑制肿瘤靶向免疫反应有关。在这里，我们讨论了DDR与炎症在肿瘤发生、肿瘤进展和对治疗的反应的背景下之间的复杂相互作用。

Significance 意义

Accumulating preclinical and clinical evidence indicates that DDR is intimately connected to the emission of immunomodulatory signals by normal and malignant cells, as part of a cell-extrinsic program to preserve organismal homeostasis. DDR-driven inflammation, however, can have diametrically opposed effects on tumor-targeting immunity. Understanding the links between the DDR and inflammation in normal and malignant cells may unlock novel immunotherapeutic paradigms to treat cancer.

越来越多的临床前期和临床证据表明，DDR作为细胞保护有机体稳态的外源性程序的一部分，与正常、恶性细胞发放免疫调节信号密切相关。然而，DDR驱动的炎症可能对肿瘤靶向免疫产生截然相反的影响。了解DDR和正常、恶性细胞中的炎症之间的联系可能会开启免疫治疗的新范式来治疗癌症。