Natural killer (NK) cells represent critical effectors of anti-tumor immune responses due to their ability to target tumor cells that escape recognition by the adaptive arm of the immune system. NK cell efficacy depends on multiple factors, including their propensity to infiltrate tumors, to reach activation threshold, and to differentiate into mature cytotoxic cells. The tumor microenvironment counteracts protective immunity by delivering anti-inflammatory signals, which stimulate the development of myeloid-derived suppressor cells (MDSC). MDSCs utilize numerous proximity-dependent and independent mechanisms to suppress functions of cytotoxic T lymphocytes and NK cells. Importantly, substantial part of their suppressive activity depends on peptidases. MDSC-derived peptidases incapacitate NK cells by shedding ligands for their activating receptors and by processing key cytokines involved in regulation of immune responses. Moreover, they are needed for sustaining the immunosuppressive loop through promotion of MDSC accumulation, expansion, and enhancement of their survival. Peptidases are at the forefront of cancer progression. However, their disparate roles in immune cells have only recently become appreciated in orchestration of the cancer immune responses. Studies that focused on elucidating the potential of peptidase inhibitors in regulation of the anti-tumor immune responses have led to renewed interest in clinical development of peptidase inhibitors. In parallel, they inspired the development of novel theranostics, that exploit increased activity of peptidases in infiltrating immune cells for targeted drug release or activation of imaging probes.

中文翻译：

---

骨髓源性抑制细胞阻碍癌症中的自然杀伤细胞活性：肽酶的作用。

自然杀伤 (NK) 细胞代表抗肿瘤免疫反应的关键效应物，因为它们能够靶向逃避免疫系统适应性臂识别的肿瘤细胞。NK 细胞的功效取决于多种因素，包括它们浸润肿瘤的倾向、达到激活阈值以及分化为成熟的细胞毒性细胞。肿瘤微环境通过传递抗炎信号来抵消保护性免疫，刺激骨髓源性抑制细胞 (MDSC) 的发育。MDSCs 利用许多接近依赖和独立的机制来抑制细胞毒性 T 淋巴细胞和 NK 细胞的功能。重要的是，它们的抑制活性的很大一部分依赖于肽酶。MDSC 衍生的肽酶通过脱落激活受体的配体和处理参与免疫反应调节的关键细胞因子，使 NK 细胞丧失能力。此外，它们是通过促进 MDSC 积累、扩展和提高其存活率来维持免疫抑制循环所必需的。肽酶处于癌症进展的最前沿。然而，它们在免疫细胞中的不同作用直到最近才在癌症免疫反应的协调中得到重视。专注于阐明肽酶抑制剂在调节抗肿瘤免疫反应中的潜力的研究已引起人们对肽酶抑制剂临床开发的新兴趣。与此同时，他们激发了新型治疗诊断学的发展，