Exploiting Human NK Cells in Tumor Therapy

Frontiers in Immunology

Maria Cristina Mingari¹  Gabriella Pietra²  Enrico Munari³  Nicola Tumino⁴  Lorenzo Moretta⁴  Paola Vacca⁴ 

[1] Department of Experimental Medicine (DIMES), Center of Excellence for Biomedical Research, Università di Genova, Genoa, Italy;Department of Experimental Medicine (DIMES), Università di Genova, Genoa, Italy;Department of Pathology, IRCCS Sacro Cuore Don Calabria, Negrar, Italy;Immunology Research Area, IRCCS Bambino Gesù Pediatric Hospital, Rome, Italy;UOC Immunology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy;

关键词: NK cells;    inhibitory checkpoints;    innate immunity;    immunotherapy;    anti-tumor therapy;   

DOI  :  10.3389/fimmu.2019.03013

来源: DOAJ

【 摘 要 】

NK cells play an important role in the innate defenses against tumor growth and metastases. Human NK cell activation and function are regulated by an array of HLA class I-specific inhibitory receptors and activating receptors recognizing ligands expressed de novo on tumor or virus-infected cells. NK cells have been exploited in immunotherapy of cancer, including: (1) the in vivo infusion of IL-2 or IL-15, cytokines inducing activation and proliferation of NK cells that are frequently impaired in cancer patients. Nonetheless, the significant toxicity experienced, primarily with IL-2, limited their use except for combination therapies, e.g., IL-15 with checkpoint inhibitors; (2) the adoptive immunotherapy with cytokine-induced NK cells had effect on some melanoma metastases (lung), while other localizations were not affected; (3) a remarkable evolution of adoptive cell therapy is represented by NK cells engineered with CAR-targeting tumor antigens (CAR-NK). CAR-NK cells complement CAR-T cells as they do not cause GvHD and may be obtained from unrelated donors. Accordingly, CAR-NK cells may represent an “off-the-shelf” tool, readily available for effective tumor therapy; (4) the efficacy of adoptive cell therapy in cancer is also witnessed by the αβT cell- and B cell-depleted haploidentical HSC transplantation in which the infusion of donor NK cells and γδT cells, together with HSC, sharply reduces leukemia relapses and infections; (5) a true revolution in tumor therapy is the use of mAbs targeting checkpoint inhibitors including PD-1, CTLA-4, the HLA class I-specific KIR, and NKG2A. Since PD-1 is expressed not only by tumor-associated T cells but also by NK cells, its blocking might unleash NK cells playing a crucial effector role against HLA class I-deficient tumors that are undetectable by T cells.

【 授权许可】

Unknown