Singh Anil K, Wu Boyang Jason
Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA.
Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA
J Immunother Cancer. 2025 Sep 9;13(9):e012567. doi: 10.1136/jitc-2025-012567.
Prostate cancer (PC) is notoriously known for exhibiting an immunologically cold phenotype in the tumor immune microenvironment (TIME), leading to the need for interventions to enhance immunotherapy efficacy. Recent findings by Zhao in the identified stromal monoamine oxidase A (MAOA), a key enzyme that degrades monoamine neurotransmitters and plays a role in the neuroendocrine system, as a critical regulator of the immune response to PC. Altering MAOA levels in myofibroblastic cancer-associated fibroblasts, either genetically or pharmacologically, can reprogram PC's TIME to modulate CD8 T cell-mediated cytotoxicity through the WNT5A-Ca²-NFATC1 signaling axis, highlighting the stromal influences on CD8 T cell cytotoxic activity within the TIME. The inactivation of MAOA synergizes with immune checkpoint blockade therapies to reverse the trajectory of prostate tumor growth. This work offers a promising therapeutic avenue for PC by positioning MAOA as a stromal modulator of immune response as well as a target for combination immunotherapies. The current commentary aims to present our perspective on how a metabolic enzyme can change the immune landscape of the tumor microenvironment, what we have learned, and what we can develop in the future.
前列腺癌（PC）因在肿瘤免疫微环境（TIME）中表现出免疫冷表型而臭名昭著，这导致需要采取干预措施来提高免疫治疗效果。赵等人最近在[具体研究]中发现，基质单胺氧化酶A（MAOA）是一种降解单胺神经递质并在神经内分泌系统中起作用的关键酶，是对PC免疫反应的关键调节因子。通过基因或药理学方法改变肌成纤维细胞癌相关成纤维细胞中的MAOA水平，可以通过WNT5A-Ca²-NFATC1信号轴重新编程PC的TIME，以调节CD8 T细胞介导的细胞毒性，突出了基质对TIME内CD8 T细胞细胞毒性活性的影响。MAOA的失活与免疫检查点阻断疗法协同作用，以逆转前列腺肿瘤生长轨迹。这项工作通过将MAOA定位为免疫反应的基质调节剂以及联合免疫疗法的靶点，为PC提供了一条有前景的治疗途径。本评论旨在阐述我们对于一种代谢酶如何改变肿瘤微环境的免疫格局、我们学到了什么以及未来可以开发什么的观点。
