Department of Immunology and Inflammation, Imperial College London, London W12 0NN, UK.
Department of Biotechnological and Applied Clinical Sciences (DISCAB), University of L'Aquila, 67100 L'Aquila, Italy.
Genes (Basel). 2024 Jan 31;15(2):197. doi: 10.3390/genes15020197.
Tumor-associated macrophages (TAMs) are the major component of the tumor microenvironment (TME), where they sustain tumor progression and or-tumor immunity. Due to their plasticity, macrophages can exhibit anti- or pro-tumor functions through the expression of different gene sets leading to distinct macrophage phenotypes: M1-like or pro-inflammatory and M2-like or anti-inflammatory. NF-κB transcription factors are central regulators of TAMs in cancers, where they often drive macrophage polarization toward an M2-like phenotype. Therefore, the NF-κB pathway is an attractive therapeutic target for cancer immunotherapy in a wide range of human tumors. Hence, targeting NF-κB pathway in the myeloid compartment is a potential clinical strategy to overcome microenvironment-induced immunosuppression and increase anti-tumor immunity. In this review, we discuss the role of NF-κB as a key driver of macrophage functions in tumors as well as the principal strategies to overcome tumor immunosuppression by targeting the NF-κB pathway.
肿瘤相关巨噬细胞（TAMs）是肿瘤微环境（TME）的主要组成部分，它们促进肿瘤进展和/或肿瘤免疫。由于其可塑性，巨噬细胞可以通过表达不同的基因集来发挥抗肿瘤或促肿瘤功能，从而导致不同的巨噬细胞表型：M1 样或促炎型和 M2 样或抗炎型。NF-κB 转录因子是癌症中 TAMs 的核心调节因子，它们通常促使巨噬细胞向 M2 样表型极化。因此，NF-κB 通路是广泛人类肿瘤癌症免疫治疗的一个有吸引力的治疗靶点。因此，针对髓系细胞中 NF-κB 通路是克服微环境诱导的免疫抑制和增强抗肿瘤免疫的潜在临床策略。在这篇综述中，我们讨论了 NF-κB 作为肿瘤中巨噬细胞功能的关键驱动因子的作用，以及通过靶向 NF-κB 通路克服肿瘤免疫抑制的主要策略。
