西班牙神经科学研究所Berta Sanchez-Laorden研究小组发现，小胶质细胞重编程增强黑色素瘤脑转移中的抗肿瘤免疫和免疫治疗反应。相关论文于2025年2月6日在线发表在《癌细胞》杂志上。

通过使用临床前模型和单细胞转录组学，研究人员发现了一种增强黑色素瘤脑转移抗肿瘤免疫的机制。研究人员发现小胶质细胞中Rela/核因子κB（NF-κB）通路的激活促进了黑色素瘤脑转移。靶向该通路能诱导小胶质细胞重编程为促炎表型，从而增强抗肿瘤免疫并减少脑转移负担。

此外，研究人员还发现黑色素瘤脑转移中的促炎小胶质细胞标志物与患者对免疫检查点抑制剂的反应改善相关，而在小鼠中靶向Rela/NF-κB通路能改善大脑中对这些治疗的反应，这提示了一种增强抗肿瘤免疫和免疫检查点抑制剂反应的策略，适用于黑色素瘤脑转移患者。

据悉，黑色素瘤是脑转移风险最高的肿瘤类型之一。然而，黑色素瘤脑转移的生物学特征以及大脑免疫微环境在治疗反应中的作用仍未完全了解。

附：英文原文

Title: Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases

Author: Francisco Javier Rodriguez-Baena, Angel Marquez-Galera, Pablo Ballesteros-Martinez, Alba Castillo, Eva Diaz, Gema Moreno-Bueno, Jose P. Lopez-Atalaya, Berta Sanchez-Laorden

Issue&Volume: 2025-02-06

Abstract: Melanoma is one of the tumor types with the highest risk of brain metastasis. However, the biology of melanoma brain metastasis and the role of the brain immune microenvironment in treatment responses are not yet fully understood. Using preclinical models and single-cell transcriptomics, we have identified a mechanism that enhances antitumor immunity in melanoma brain metastasis. We show that activation of the Rela/Nuclear Factor κB (NF-κB) pathway in microglia promotes melanoma brain metastasis. Targeting this pathway elicits microglia reprogramming toward a proinflammatory phenotype, which enhances antitumor immunity and reduces brain metastatic burden. Furthermore, we found that proinflammatory microglial markers in melanoma brain metastasis are associated with improved responses to immune checkpoint inhibitors in patients and targeting Rela/NF-κB pathway in mice improves responses to these therapies in the brain, suggesting a strategy to enhance antitumor immunity and responses to immune checkpoint inhibitors in patients with melanoma brain metastasis.

DOI: 10.1016/j.ccell.2025.01.008

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00026-1