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Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors
Despite advances in the diagnostic and therapeutic modalities, the prognosis of several solid tumor malignancies remains poor. Different factors associated with solid tumors including a varied genetic signature, complex molecular signaling pathways, defective cross talk between the tumor cells and i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378304/ https://www.ncbi.nlm.nih.gov/pubmed/30805309 http://dx.doi.org/10.3389/fonc.2019.00051 |
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author | Nayyar, Gaurav Chu, Yaya Cairo, Mitchell S. |
author_facet | Nayyar, Gaurav Chu, Yaya Cairo, Mitchell S. |
author_sort | Nayyar, Gaurav |
collection | PubMed |
description | Despite advances in the diagnostic and therapeutic modalities, the prognosis of several solid tumor malignancies remains poor. Different factors associated with solid tumors including a varied genetic signature, complex molecular signaling pathways, defective cross talk between the tumor cells and immune cells, hypoxic and immunosuppressive effects of tumor microenvironment result in a treatment resistant and metastatic phenotype. Over the past several years, immunotherapy has emerged as an attractive therapeutic option against multiple malignancies. The unique ability of natural killer (NK) cells to target cancer cells without antigen specificity makes them an ideal candidate for use against solid tumors. However, the outcomes of adoptive NK cell infusions into patients with solid tumors have been disappointing. Extensive studies have been done to investigate different strategies to improve the NK cell function, trafficking and tumor targeting. Use of cytokines and cytokine analogs has been well described and utilized to enhance the proliferation, stimulation and persistence of NK cells. Other techniques like blocking the human leukocyte antigen-killer cell receptors (KIR) interactions with anti-KIR monoclonal antibodies, preventing CD16 receptor shedding, increasing the expression of activating NK cell receptors like NKG2D, and use of immunocytokines and immune checkpoint inhibitors can enhance NK cell mediated cytotoxicity. Using genetically modified NK cells with chimeric antigen receptors and bispecific and trispecific NK cell engagers, NK cells can be effectively redirected to the tumor cells improving their cytotoxic potential. In this review, we have described these strategies and highlighted the need to further optimize these strategies to improve the clinical outcome of NK cell based immunotherapy against solid tumors. |
format | Online Article Text |
id | pubmed-6378304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63783042019-02-25 Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors Nayyar, Gaurav Chu, Yaya Cairo, Mitchell S. Front Oncol Oncology Despite advances in the diagnostic and therapeutic modalities, the prognosis of several solid tumor malignancies remains poor. Different factors associated with solid tumors including a varied genetic signature, complex molecular signaling pathways, defective cross talk between the tumor cells and immune cells, hypoxic and immunosuppressive effects of tumor microenvironment result in a treatment resistant and metastatic phenotype. Over the past several years, immunotherapy has emerged as an attractive therapeutic option against multiple malignancies. The unique ability of natural killer (NK) cells to target cancer cells without antigen specificity makes them an ideal candidate for use against solid tumors. However, the outcomes of adoptive NK cell infusions into patients with solid tumors have been disappointing. Extensive studies have been done to investigate different strategies to improve the NK cell function, trafficking and tumor targeting. Use of cytokines and cytokine analogs has been well described and utilized to enhance the proliferation, stimulation and persistence of NK cells. Other techniques like blocking the human leukocyte antigen-killer cell receptors (KIR) interactions with anti-KIR monoclonal antibodies, preventing CD16 receptor shedding, increasing the expression of activating NK cell receptors like NKG2D, and use of immunocytokines and immune checkpoint inhibitors can enhance NK cell mediated cytotoxicity. Using genetically modified NK cells with chimeric antigen receptors and bispecific and trispecific NK cell engagers, NK cells can be effectively redirected to the tumor cells improving their cytotoxic potential. In this review, we have described these strategies and highlighted the need to further optimize these strategies to improve the clinical outcome of NK cell based immunotherapy against solid tumors. Frontiers Media S.A. 2019-02-11 /pmc/articles/PMC6378304/ /pubmed/30805309 http://dx.doi.org/10.3389/fonc.2019.00051 Text en Copyright © 2019 Nayyar, Chu and Cairo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Nayyar, Gaurav Chu, Yaya Cairo, Mitchell S. Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors |
title | Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors |
title_full | Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors |
title_fullStr | Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors |
title_full_unstemmed | Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors |
title_short | Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors |
title_sort | overcoming resistance to natural killer cell based immunotherapies for solid tumors |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378304/ https://www.ncbi.nlm.nih.gov/pubmed/30805309 http://dx.doi.org/10.3389/fonc.2019.00051 |
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