Department of Inflammology, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
Int Immunol. 2021 Nov 25;33(12):841-846. doi: 10.1093/intimm/dxab050.
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 (DAMP) molecules 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.
正如免疫疗法在提高生存率方面的成功所临床证明的那样，肿瘤通过规避免疫监视获得生存优势。其一个明确的特征是创建和维持肿瘤免疫微环境（TIME），通过多种机制直接和间接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深入研究的领域，例如鉴定和表征肿瘤细胞主动和被动释放的可调节免疫细胞功能的可溶性因子。特别是，损伤相关分子模式（DAMP）分子通常由坏死肿瘤细胞释放，被先天免疫受体（如 Toll 样受体（TLR））识别，并刺激 TIME 内的免疫细胞。鉴于它们对免疫系统的广泛而强大的影响，更好地了解 DAMP 和 TLR 相互作用如何塑造 TIME 以促进肿瘤生长，将为癌症免疫疗法确定新的策略和方法。
