Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors

Introduction: Natural killer (NK) cells are innate lymphoid cells capable of directly killing target cells while modulating immune effector responses. Despite their multifunctional capacities, a limited understanding of their plasticity and heterogeneity has impeded progress in developing...

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Main Authors: Zerick Terrell Dunbar, Salvador González-Ochoa, Thanigaivelan Kanagasabai, Alla Ivanova, Anil Shanker
Format: Article
Language:English
Published: Karger Publishers 2024-01-01
Series:Journal of Innate Immunity
Online Access:https://karger.com/article/doi/10.1159/000542078
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author Zerick Terrell Dunbar
Salvador González-Ochoa
Thanigaivelan Kanagasabai
Alla Ivanova
Anil Shanker
author_facet Zerick Terrell Dunbar
Salvador González-Ochoa
Thanigaivelan Kanagasabai
Alla Ivanova
Anil Shanker
author_sort Zerick Terrell Dunbar
collection DOAJ
description Introduction: Natural killer (NK) cells are innate lymphoid cells capable of directly killing target cells while modulating immune effector responses. Despite their multifunctional capacities, a limited understanding of their plasticity and heterogeneity has impeded progress in developing effective NK cell-based cancer therapies. In this study, we investigated NK cell tissue heterogeneity in relation to their phenotype and effector functions against lung tumors. Methods: Using hanging drop tumor spheroid and subcutaneously established LL/2 (LLC1) lung tumor models, we examined NK cell receptor diversity and its correlation with tissue-specific cytotoxicity through multiparametric flow cytometry, fluorescence imaging, and cytotoxicity assays. Results: We identified distinct patterns of cell surface receptors expression on tissue-specific NK cells that are crucial for antitumor activity. Linear regression mathematical analyses further revealed significant positive correlations between activation-associated cell surface receptors and cytotoxic capacity in NK cells from tissues such as the liver and bone marrow. Conclusion: These findings underscore the differential effector capacities of NK cells from distinct tissues, even prior to exposure to LL/2 tumor cells. This highlights the significance of tissue-specific NK cell heterogeneity and its impact on their antitumor cytotoxicity. Recognizing these distinct tissue-specific receptor expression patterns will be instrumental in developing more efficacious NK cell-based cancer treatments.
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spelling doaj-art-13ee3a276ef349f683dbb7e46acbd6012025-08-20T03:09:47ZengKarger PublishersJournal of Innate Immunity1662-81282024-01-0116157359410.1159/000542078Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung TumorsZerick Terrell DunbarSalvador González-OchoaThanigaivelan KanagasabaiAlla IvanovaAnil Shanker Introduction: Natural killer (NK) cells are innate lymphoid cells capable of directly killing target cells while modulating immune effector responses. Despite their multifunctional capacities, a limited understanding of their plasticity and heterogeneity has impeded progress in developing effective NK cell-based cancer therapies. In this study, we investigated NK cell tissue heterogeneity in relation to their phenotype and effector functions against lung tumors. Methods: Using hanging drop tumor spheroid and subcutaneously established LL/2 (LLC1) lung tumor models, we examined NK cell receptor diversity and its correlation with tissue-specific cytotoxicity through multiparametric flow cytometry, fluorescence imaging, and cytotoxicity assays. Results: We identified distinct patterns of cell surface receptors expression on tissue-specific NK cells that are crucial for antitumor activity. Linear regression mathematical analyses further revealed significant positive correlations between activation-associated cell surface receptors and cytotoxic capacity in NK cells from tissues such as the liver and bone marrow. Conclusion: These findings underscore the differential effector capacities of NK cells from distinct tissues, even prior to exposure to LL/2 tumor cells. This highlights the significance of tissue-specific NK cell heterogeneity and its impact on their antitumor cytotoxicity. Recognizing these distinct tissue-specific receptor expression patterns will be instrumental in developing more efficacious NK cell-based cancer treatments. https://karger.com/article/doi/10.1159/000542078
spellingShingle Zerick Terrell Dunbar
Salvador González-Ochoa
Thanigaivelan Kanagasabai
Alla Ivanova
Anil Shanker
Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors
Journal of Innate Immunity
title Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors
title_full Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors
title_fullStr Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors
title_full_unstemmed Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors
title_short Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors
title_sort differential effector function of tissue specific natural killer cells against lung tumors
url https://karger.com/article/doi/10.1159/000542078
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AT allaivanova differentialeffectorfunctionoftissuespecificnaturalkillercellsagainstlungtumors
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