Garofalo Cinzia, Cerantonio Annamaria, Muscoli Carolina, Mollace Vincenzo, Viglietto Giuseppe, De Marco Carmela, Cristiani Costanza Maria
Department of Experimental and Clinical Medicine, "Magna Græcia" University of Catanzaro, 88100 Catanzaro, Italy.
Department of Health Science, Institute of Research for Food Safety & Health (IRC-FSH), "Magna Græcia" University of Catanzaro, 88100 Catanzaro, Italy.
Cancers (Basel). 2023 Feb 1;15(3):933. doi: 10.3390/cancers15030933.
Immune checkpoint inhibitors (ICIs) and targeted therapy have dramatically changed the outcome of metastatic melanoma patients. Although immune checkpoints were developed based on the biology of adaptive T cells, they have subsequently been shown to be expressed by other subsets of immune cells. Similarly, the immunomodulatory properties of targeted therapy have been studied primarily with respect to T lymphocytes, but other subsets of immune cells could be affected. Innate lymphoid cells (ILCs) are considered the innate counterpart of T lymphocytes and include cytotoxic natural killer cells, as well as three helper subsets, ILC1, ILC2 and ILC3. Thanks to their tissue distribution and their ability to respond rapidly to environmental stimuli, ILCs play a central role in shaping immunity. While the role of NK cells in melanoma physiopathology and therapy is well established, little is known about the other helper ILC subsets. In this review, we summarize recent findings on the ability of the melanoma TME to influence the phenotype and functional plasticity of helper ILCs and highlight how this subset may in turn shape the TME. We also discuss changes in the melanoma TME induced by targeted therapy that could affect helper ILC functions, the expression of immune checkpoints on this subset and how their inhibition by ICIs may modulate helper ILC function and contribute to therapeutic efficacy.
免疫检查点抑制剂（ICIs）和靶向治疗显著改变了转移性黑色素瘤患者的治疗结局。尽管免疫检查点是基于适应性T细胞的生物学特性开发的，但随后发现它们也在其他免疫细胞亚群中表达。同样，靶向治疗的免疫调节特性主要是针对T淋巴细胞进行研究的，但其他免疫细胞亚群也可能受到影响。固有淋巴细胞（ILCs）被认为是T淋巴细胞的固有对应物，包括细胞毒性自然杀伤细胞以及三个辅助亚群，即ILC1、ILC2和ILC3。由于其组织分布以及对环境刺激快速做出反应的能力，ILCs在塑造免疫方面发挥着核心作用。虽然NK细胞在黑色素瘤病理生理学和治疗中的作用已得到充分证实，但对于其他辅助性ILC亚群的了解却很少。在这篇综述中，我们总结了黑色素瘤肿瘤微环境（TME）影响辅助性ILCs表型和功能可塑性能力的最新研究结果，并强调了该亚群如何反过来塑造TME。我们还讨论了靶向治疗引起的黑色素瘤TME变化，这些变化可能影响辅助性ILCs功能、该亚群上免疫检查点的表达，以及ICIs对它们的抑制如何调节辅助性ILCs功能并有助于提高治疗效果。
