NK Cells in the Tumor Microenvironment
Natural killer cells are powerful effectors of innate immunity that constitute a first line of defense against cancer. NK cells express an array of germline-encoded receptors which allow them to eliminate transformed cells and spare normal, healthy cells.
- PDF / 804,536 Bytes
- 22 Pages / 504.567 x 720 pts Page_size
- 109 Downloads / 227 Views
NK Cells in the Tumor Microenvironment Camille Guillerey
Abstract
Natural killer cells are powerful effectors of innate immunity that constitute a first line of defense against cancer. NK cells express an array of germline-encoded receptors which allow them to eliminate transformed cells and spare normal, healthy cells. Owing to their ability to kill circulating tumor cells, NK cells play a major role in the protection against cancer metastases. There is also convincing evidence that NK cells protect against some hematological cancers such as acute myeloid leukemia. However, the importance of NK cells for the control of established solid tumors is rather uncertain. Several mechanisms impede NK cell-mediated elimination of solid tumors, starting with the incapacity of NK cells to infiltrate the core of the tumor. In addition, immune escape mechanisms are at play in both solid and hematological cancers. These include the immunoediting of tumor cells and aberrant chronic inflammation that renders NK cells ineffective. In this chapter, I review the phenotypic characteristics of NK cells within the tumor microenvironment. C. Guillerey (*) Cancer Immunotherapies Laboratory, Mater Research Institute, The University of Queensland, Translational Research Institute, Brisbane, QLD, Australia e-mail: [email protected]
Furthermore, I describe the mechanisms by which NK cells contribute to antitumor immunity. Finally, I review the different immune- evasion factors that impair NK cell activity against cancer. Keywords
Natural killer cells · Cancer immunology · Innate immunity · Immune escape · Immunoediting · Immunosurveillance · Immunotherapy · NK cell receptors · Cytokines · Metastases · Leukemia · T cells · Dendritic cells · ILCs · Immune checkpoints
4.1
Introduction
Natural killer (NK) cells are the cytotoxic members of the innate lymphoid cell (ILC) family [49]. They were discovered in the mid-1970s for their ability to rapidly kill tumor cells without pre-activation [69, 70]. In opposition to other ILCs which are tissue resident, NK cells are blood-circulating cells that screen our body for damaged or stressed cells. Because they can detect and respond immediately to the very early signs of tumor transformation or infection, NK cells constitute a first line of defense against viruses and cancer [136].
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2020 A. Birbrair (ed.), Tumor Microenvironment, Advances in Experimental Medicine and Biology 1273, https://doi.org/10.1007/978-3-030-49270-0_4
69
C. Guillerey
70
Belonging to the innate immune system, NK cells are devoid of recombination activating gene (RAG)-rearranged receptors and do not mediate antigen-specific responses. Instead, the molecular basis for NK cell-mediated recognition of tumor cells is ensured by a panel of germline- encoded surface receptors [88]. Some of these receptors bind to stress-induced molecules and transmit activation signals, while other deliver inhibitory
Data Loading...
