Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies.
Influencing tumor-associated macrophages in malignant melanoma with monoclonal antibodies.
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DOI：
10.1080/2162402x.2022.2127284
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发表时间：
2022
期刊：
影响因子：
7.2
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中科院分区：
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在过去的十年中，单克隆抗体（mAb）治疗黑色素瘤的应用显着改善了这种恶性肿瘤的临床管理。目前批准的用于黑色素瘤的mAb通过阻断免疫检查点分子PD-L1/PD-1和CTLA-4来增强T细胞效应物免疫应答。然而，超过一半的患者没有从治疗中获益。靶向肿瘤微环境中突出的髓样区室，特别是一直丰富的肿瘤相关巨噬细胞（TAM），可能是补充现有疗法并提高治疗成功率的有希望的策略。TAM是一种高度多样化和可塑性的细胞亚群，其促肿瘤特性可以支持黑色素瘤生长、血管生成和侵袭。了解它们在癌症中的多样性，可塑性和多方面作用，为新的有前途的以TAM为中心的治疗策略奠定了基础。在治疗环境中，巨噬细胞可以通过多种机制被抗体靶向，包括通过消耗、抑制特定的促肿瘤特性、差异极化至促炎状态和增强抗肿瘤免疫功能。在这里，我们讨论了黑色素瘤中的TAM，它们与检查点抑制剂抗体的相互作用，以及针对TAM生物学不同方面的新兴mAb及其转化为临床的潜力。
The application of monoclonal antibodies (mAbs) for the treatment of melanoma has significantly improved the clinical management of this malignancy over the last decade. Currently approved mAbs for melanoma enhance T cell effector immune responses by blocking immune checkpoint molecules PD-L1/PD-1 and CTLA-4. However, more than half of patients do not benefit from treatment. Targeting the prominent myeloid compartment within the tumor microenvironment, and in particular the ever-abundant tumor-associated macrophages (TAMs), may be a promising strategy to complement existing therapies and enhance treatment success. TAMs are a highly diverse and plastic subset of cells whose pro-tumor properties can support melanoma growth, angiogenesis and invasion. Understanding of their diversity, plasticity and multifaceted roles in cancer forms the basis for new promising TAM-centered treatment strategies. There are multiple mechanisms by which macrophages can be targeted with antibodies in a therapeutic setting, including by depletion, inhibition of specific pro-tumor properties, differential polarization to pro-inflammatory states and enhancement of antitumor immune functions. Here, we discuss TAMs in melanoma, their interactions with checkpoint inhibitor antibodies and emerging mAbs targeting different aspects of TAM biology and their potential to be translated to the clinic.