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Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment

The ability to expand and activate natural Killer (NK) cells ex vivo has dramatically changed the landscape in the development of novel adoptive cell therapies for treating cancer over the last decade. NK cells have become a key player for cancer immunotherapy due to their innate ability to kill mal...

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Autores principales: Portillo, Ana L., Monteiro, Jonathan K., Rojas, Eduardo A., Ritchie, Tyrah M., Gillgrass, Amy, Ashkar, Ali A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663242/
https://www.ncbi.nlm.nih.gov/pubmed/38022679
http://dx.doi.org/10.3389/fimmu.2023.1286750
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author Portillo, Ana L.
Monteiro, Jonathan K.
Rojas, Eduardo A.
Ritchie, Tyrah M.
Gillgrass, Amy
Ashkar, Ali A.
author_facet Portillo, Ana L.
Monteiro, Jonathan K.
Rojas, Eduardo A.
Ritchie, Tyrah M.
Gillgrass, Amy
Ashkar, Ali A.
author_sort Portillo, Ana L.
collection PubMed
description The ability to expand and activate natural Killer (NK) cells ex vivo has dramatically changed the landscape in the development of novel adoptive cell therapies for treating cancer over the last decade. NK cells have become a key player for cancer immunotherapy due to their innate ability to kill malignant cells while not harming healthy cells, allowing their potential use as an “off-the-shelf” product. Furthermore, recent advancements in NK cell genetic engineering methods have enabled the efficient generation of chimeric antigen receptor (CAR)-expressing NK cells that can exert both CAR-dependent and antigen-independent killing. Clinically, CAR-NK cells have shown promising efficacy and safety for treating CD19-expressing hematologic malignancies. While the number of pre-clinical studies using CAR-NK cells continues to expand, it is evident that solid tumors pose a unique challenge to NK cell-based adoptive cell therapies. Major barriers for efficacy include low NK cell trafficking and infiltration into solid tumor sites, low persistence, and immunosuppression by the harsh solid tumor microenvironment (TME). In this review we discuss the barriers posed by the solid tumor that prevent immune cell trafficking and NK cell effector functions. We then discuss promising strategies to enhance NK cell infiltration into solid tumor sites and activation within the TME. This includes NK cell-intrinsic and -extrinsic mechanisms such as NK cell engineering to resist TME-mediated inhibition and use of tumor-targeted agents such as oncolytic viruses expressing chemoattracting and activating payloads. We then discuss opportunities and challenges for using combination therapies to extend NK cell therapies for the treatment of solid tumors.
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spelling pubmed-106632422023-01-01 Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment Portillo, Ana L. Monteiro, Jonathan K. Rojas, Eduardo A. Ritchie, Tyrah M. Gillgrass, Amy Ashkar, Ali A. Front Immunol Immunology The ability to expand and activate natural Killer (NK) cells ex vivo has dramatically changed the landscape in the development of novel adoptive cell therapies for treating cancer over the last decade. NK cells have become a key player for cancer immunotherapy due to their innate ability to kill malignant cells while not harming healthy cells, allowing their potential use as an “off-the-shelf” product. Furthermore, recent advancements in NK cell genetic engineering methods have enabled the efficient generation of chimeric antigen receptor (CAR)-expressing NK cells that can exert both CAR-dependent and antigen-independent killing. Clinically, CAR-NK cells have shown promising efficacy and safety for treating CD19-expressing hematologic malignancies. While the number of pre-clinical studies using CAR-NK cells continues to expand, it is evident that solid tumors pose a unique challenge to NK cell-based adoptive cell therapies. Major barriers for efficacy include low NK cell trafficking and infiltration into solid tumor sites, low persistence, and immunosuppression by the harsh solid tumor microenvironment (TME). In this review we discuss the barriers posed by the solid tumor that prevent immune cell trafficking and NK cell effector functions. We then discuss promising strategies to enhance NK cell infiltration into solid tumor sites and activation within the TME. This includes NK cell-intrinsic and -extrinsic mechanisms such as NK cell engineering to resist TME-mediated inhibition and use of tumor-targeted agents such as oncolytic viruses expressing chemoattracting and activating payloads. We then discuss opportunities and challenges for using combination therapies to extend NK cell therapies for the treatment of solid tumors. Frontiers Media S.A. 2023-11-08 /pmc/articles/PMC10663242/ /pubmed/38022679 http://dx.doi.org/10.3389/fimmu.2023.1286750 Text en Copyright © 2023 Portillo, Monteiro, Rojas, Ritchie, Gillgrass and Ashkar https://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 Immunology
Portillo, Ana L.
Monteiro, Jonathan K.
Rojas, Eduardo A.
Ritchie, Tyrah M.
Gillgrass, Amy
Ashkar, Ali A.
Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment
title Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment
title_full Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment
title_fullStr Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment
title_full_unstemmed Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment
title_short Charting a killer course to the solid tumor: strategies to recruit and activate NK cells in the tumor microenvironment
title_sort charting a killer course to the solid tumor: strategies to recruit and activate nk cells in the tumor microenvironment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663242/
https://www.ncbi.nlm.nih.gov/pubmed/38022679
http://dx.doi.org/10.3389/fimmu.2023.1286750
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