Cazzetta Valentina, Depierreux Delphine, Colucci Francesco, Mikulak Joanna, Mavilio Domenico
Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy.
Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy.
Cancers (Basel). 2023 Feb 16;15(4):1264. doi: 10.3390/cancers15041264.
Immune regulation has revolutionized cancer treatment with the introduction of T-cell-targeted immune checkpoint inhibitors (ICIs). This successful immunotherapy has led to a more complete view of cancer that now considers not only the cancer cells to be targeted and destroyed but also the immune environment of the cancer cells. Current challenges associated with the enhancement of ICI effects are increasing the fraction of responding patients through personalized combinations of multiple ICIs and overcoming acquired resistance. This requires a complete overview of the anti-tumor immune response, which depends on a complex interplay between innate and adaptive immune cells with the tumor microenvironment. The NKG2A was revealed to be a key immune checkpoint for both Natural Killer (NK) cells and T cells. Monalizumab, a humanized anti-NKG2A antibody, enhances NK cell activity against various tumor cells and rescues CD8 αβ T cell function in combination with PD-1/PD-L1 blockade. In this review, we discuss the potential for targeting NKG2A expressed on tumor-sensing human γδ T cells, mostly on the specific Vδ2 T cell subset, in order to emphasize its importance and potential in the development of new ICI-based therapeutic approaches.
免疫调节通过引入靶向T细胞的免疫检查点抑制剂（ICI）彻底改变了癌症治疗。这种成功的免疫疗法使人们对癌症有了更全面的认识，现在不仅要考虑靶向和摧毁癌细胞，还要考虑癌细胞的免疫环境。当前与增强ICI疗效相关的挑战包括通过多种ICI的个性化联合来增加应答患者的比例以及克服获得性耐药。这需要全面了解抗肿瘤免疫反应，而这取决于先天性和适应性免疫细胞与肿瘤微环境之间的复杂相互作用。NKG2A被发现是自然杀伤（NK）细胞和T细胞的关键免疫检查点。莫那利珠单抗是一种人源化抗NKG2A抗体，可增强NK细胞对各种肿瘤细胞的活性，并与PD-1/PD-L1阻断联合挽救CD8αβT细胞功能。在本综述中，我们讨论了靶向肿瘤感知人γδT细胞（主要是特定的Vδ2T细胞亚群）上表达的NKG2A的潜力，以强调其在基于ICI的新治疗方法开发中的重要性和潜力。
