Department of Oncology, Mayo Clinic, Rochester, MN, USA.
Department of Oncology, Mayo Clinic, Rochester, MN, USA; Mayo Clinic Cancer Center, Mayo Clinic, Rochester, MN, USA.
Trends Immunol. 2023 Sep;44(9):724-743. doi: 10.1016/j.it.2023.07.002. Epub 2023 Aug 10.
The natural history of advanced malignant melanoma demonstrates that, in most cases, widespread tumor dissemination is preceded by regional metastases involving tumor-draining lymph nodes [sentinel lymph nodes (SLNs)]. Under physiological conditions, LNs play a central role in immunosurveillance to non-self-antigens to which they are exposed via afferent lymph. The dysfunctional immunity in SLNs is mediated by tumor secretory factors that allow the survival of metastatic melanoma cells within the LN by creating a premetastatic niche (PMN). Recent studies outline the altered microenvironment of LNs shaped by melanoma mediators. Here, we discuss tumor secretory factors involved in subverting tumor immunity and remodeling LNs and highlight emerging therapeutic strategies to reinvigorate antitumoral immunity in SLNs.
晚期恶性黑色素瘤的自然病程表明,在大多数情况下,广泛的肿瘤播散之前,区域转移会累及引流肿瘤的淋巴结[前哨淋巴结 (SLN)]。在生理条件下,淋巴结在针对其通过输入淋巴管暴露的非自身抗原的免疫监视中发挥核心作用。SLN 中的功能障碍性免疫是由肿瘤分泌因子介导的,这些因子通过创建预先转移的生态位 (PMN),允许转移黑色素瘤细胞在淋巴结内存活。最近的研究概述了由黑色素瘤介质塑造的改变的淋巴结微环境。在这里,我们讨论了参与颠覆肿瘤免疫和重塑淋巴结的肿瘤分泌因子,并强调了新兴的治疗策略,以重新激活 SLN 中的抗肿瘤免疫。