Abstract

As clinically demonstrated by the success of immunotherapies to improve survival outcomes, tumors are known to gain a survival advantage by circumventing immune surveillance. A defining feature of this is the creation and maintenance of a tumor immune microenvironment (TIME) that directly and indirectly alters the host’s immunologic signaling pathways through a variety of mechanisms. Tumor-intrinsic mechanisms that instruct the formation and maintenance of the TIME have been an area of intensive study, such as the identification and characterization of soluble factors actively and passively released by tumor cells that modulate immune cell function. In particular, damage-associated molecular pattern molecules (DAMPs) typically released by necrotic tumor cells are recognized by innate immune receptors such as Toll-like receptors (TLRs) and stimulate immune cells within TIME. Given their broad and potent effects on the immune system, a better understanding for how DAMP and TLR interactions sculpt the TIME to favor tumor growth would identify new strategies and approaches for cancer immunotherapy.

中文翻译：

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肿瘤免疫微环境中的损伤相关分子模式和Toll样受体

摘要

正如临床上免疫疗法成功改善生存结果所证明的那样，众所周知，肿瘤可以通过绕过免疫监视来获得生存优势。这方面的一个决定性特征是肿瘤免疫微环境 (TIME) 的创建和维护，该微环境通过多种机制直接和间接地改变宿主的免疫信号通路。指导 TIME 形成和维持的肿瘤内在机制一直是一个深入研究的领域，例如识别和表征由调节免疫细胞功能的肿瘤细胞主动和被动释放的可溶性因子。特别是，通常由坏死肿瘤细胞释放的损伤相关分子模式分子 (DAMP) 被 Toll 样受体 (TLR) 等先天免疫受体识别并在 TIME 内刺激免疫细胞。鉴于它们对免疫系统的广泛而有效的影响，更好地了解 DAMP 和 TLR 相互作用如何塑造 TIME 以促进肿瘤生长将确定癌症免疫治疗的新策略和方法。