Natural killer cells in cancer biology and therapy

• Published in: Molecular cancer Vol. 19; no. 1; pp. 120 - 26
• Main Authors: Wu, Song-Yang, Fu, Tong, Jiang, Yi-Zhou, Shao, Zhi-Ming
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 06.08.2020; BioMed Central; BMC
• Subjects: Adaptive immunity; Animals; Antigens; Biology; Biomarkers; Bone marrow; Cancer; Cancer therapies; Cancer treatment; Cytokines; Cytotoxicity; Development and progression; Disease Management; Disease Progression; Disease Susceptibility; Effector cells; Energy Metabolism; Genetic engineering; Genetically modified organisms; Health aspects; Humans; Immunity, Innate; Immunoglobulins; Immunometabolism; Immunomodulation; Immunotherapy; Innate immunity; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Killer Cells, Natural - pathology; Ligands; Lymphatic system; Lymphocytes; Lymphocytes T; Metastases; Metastasis; Natural killer cell; Natural killer cells; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; Precision treatment; Proteins; Review; Signal Transduction; Spleen; T cell receptors; Thymus gland; Tumor Microenvironment - immunology; Tumor progression; Natural killer cell; Immunometabolism; Innate immunity; Precision treatment; Immunotherapy; Tumor progression
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-020-01238-x

The tumor microenvironment is highly complex, and immune escape is currently considered an important hallmark of cancer, largely contributing to tumor progression and metastasis. Named for their capability of killing target cells autonomously, natural killer (NK) cells serve as the main effector cells toward cancer in innate immunity and are highly heterogeneous in the microenvironment. Most current treatment options harnessing the tumor microenvironment focus on T cell-immunity, either by promoting activating signals or suppressing inhibitory ones. The limited success achieved by T cell immunotherapy highlights the importance of developing new-generation immunotherapeutics, for example utilizing previously ignored NK cells. Although tumors also evolve to resist NK cell-induced cytotoxicity, cytokine supplement, blockade of suppressive molecules and genetic engineering of NK cells may overcome such resistance with great promise in both solid and hematological malignancies. In this review, we summarized the fundamental characteristics and recent advances of NK cells within tumor immunometabolic microenvironment, and discussed potential application and limitations of emerging NK cell-based therapeutic strategies in the era of presicion medicine.