Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Immunol. 2023 Oct 23;14:1244170. doi: 10.3389/fimmu.2023.1244170. eCollection 2023.
Immunotherapy is a promising therapeutic tool that promotes the elimination of cancerous cells by a patient's own immune system. However, in the clinical setting, the number of cancer patients benefitting from immunotherapy is limited. Identification and targeting of other immune subsets, such as tumor-associated macrophages, and alternative immune checkpoints, like Mer, may further limit tumor progression and therapy resistance. In this review, we highlight the key roles of macrophage Mer signaling in immune suppression. We also summarize the role of pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes in tumor onset and progression and how Mer structure and activation can be targeted therapeutically to alter activation state. Preclinical and clinical studies focusing on Mer kinase inhibition have demonstrated the potential of targeting this innate immune checkpoint, leading to improved anti-tumor responses and patient outcomes.
免疫疗法是一种有前途的治疗工具，它通过患者自身的免疫系统促进癌细胞的消除。然而，在临床环境中，受益于免疫疗法的癌症患者数量有限。鉴定和靶向其他免疫亚群，如肿瘤相关巨噬细胞，以及替代免疫检查点，如 Mer，可能会进一步限制肿瘤的进展和治疗耐药性。在这篇综述中，我们强调了巨噬细胞 Mer 信号在免疫抑制中的关键作用。我们还总结了促炎（M1）和抗炎（M2）表型在肿瘤发生和进展中的作用，以及 Mer 结构和激活如何被靶向治疗以改变激活状态。专注于 Mer 激酶抑制的临床前和临床研究表明，靶向这种先天免疫检查点具有改善抗肿瘤反应和患者预后的潜力。
