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癌症中凝血与炎症的相互作用:局限性与治疗机会。

Interplay between coagulation and inflammation in cancer: Limitations and therapeutic opportunities.

机构信息

Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Dermatology, Venereology and Allergology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Department of Dermatology and Venereology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Cancer Treat Rev. 2022 Jan;102:102322. doi: 10.1016/j.ctrv.2021.102322. Epub 2021 Dec 1.

Abstract

Advances in understanding the molecular mechanisms of tumor progression have achieved impressive progress in the treatment of cancer and so-called immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Indeed, antibody-based drugs blocking immune escape of tumor cells by modulation of T cell responses are increasingly utilized for a wide range of tumor entities. Nonetheless, response rates remain limited, and the development of secondary resistance is a common problem. In addition, by increasing the immune response a variety of severe side effects are provoked. Next to autoimmune responses, activation of the complement system and skin toxicity, an increased incidence for thrombotic complications has been observed associated with an increased mortality rate. Based on this, it can be postulated that the interplay of coagulation with inflammation in the tumor microenvironment is relevant for each step in the tumor life cycle. This review focuses on the coagulation as central player fostering mechanisms associated with tumor progression. Thus, a better understanding of the molecular pathways involved in the complex interaction of circulating tumor cells, the plasmatic coagulation and immune cells may help to improve therapeutic concepts reducing mortality and morbidity associated with cancer.

摘要

在理解肿瘤进展的分子机制方面取得的进展,在癌症治疗方面取得了令人瞩目的进展,所谓的免疫检查点抑制剂(ICIs)已经彻底改变了癌症治疗。事实上,通过调节 T 细胞反应来阻断肿瘤细胞免疫逃逸的基于抗体的药物越来越多地用于广泛的肿瘤实体。尽管如此,反应率仍然有限,继发性耐药的发展是一个常见的问题。此外,通过增强免疫反应,会引发各种严重的副作用。除了自身免疫反应、补体系统激活和皮肤毒性外,还观察到与死亡率增加相关的血栓并发症发生率增加。基于此,可以假设凝血与肿瘤微环境中的炎症之间的相互作用与肿瘤生命周期的每个步骤都有关。本综述重点关注凝血作为核心参与者促进与肿瘤进展相关的机制。因此,更好地了解循环肿瘤细胞、血浆凝血和免疫细胞之间复杂相互作用中涉及的分子途径,可能有助于改善治疗概念,降低与癌症相关的死亡率和发病率。

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