NK cells and ILCs in tumor immunotherapy

作者：Simona Sivori, Daniela Pende, Linda Quatrini, Gabriella Pietra, Mariella Della Chiesa, Paola Vacca, Nicola Tumino, Francesca Moretta, Maria Cristina Mingari, Franco Locatelli, Lorenzo Moretta · 发表于：Molecular Aspects of Medicine · 年份：2020 · DOI：10.1016/j.mam.2020.100870 · 被引用次数：281 · 研究领域：Immune Cell Function and Interaction、IL-33, ST2, and ILC Pathways、Autoimmune and Inflammatory Disorders Research

Cells of the innate immunity play an important role in tumor immunotherapy. Thus, NK cells can control tumor growth and metastatic spread. Thanks to their strong cytolytic activity against tumors, different approaches have been developed for exploiting/harnessing their function in patients with leukemia or solid tumors. Pioneering trials were based on the adoptive transfer of autologous NK cell-enriched cell populations that were expanded in vitro and co-infused with IL-2. Although relevant results were obtained in patients with advanced melanoma, the effect was mostly limited to certain metastatic localizations, particularly to the lung. In addition, the severe IL-2-related toxicity and the preferential IL-2-induced expansion of Treg limited this type of approach. This limitation may be overcome by the use of IL-15, particularly of modified IL-15 molecules to improve its half-life and optimize the biological effects. Other approaches to harness NK cell function include stimulation via TLR, the use of bi- and tri-specific NK cell engagers (BiKE and TriKE) linking activating NK receptors (e.g. CD16) to tumor-associated antigens and even incorporating an IL-15 moiety (TriKE). As recently shown, in tumor patients, NK cells may also express inhibitory checkpoints, primarily PD-1. Accordingly, the therapeutic use of checkpoint inhibitors may unleash NK cells against PD-L1+ tumors. This effect may be predominant and crucial in tumors that have lost HLA cl-I expression, thus resulti...