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

Abstract: 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Differential Effector Function of Tissue-Specific Natural Killer Cells against Lung Tumors ; volume:16 ; number:1 ; year:2024 ; pages:573-594 ; extent:22
Journal of innate immunity ; 16, Heft 1 (2024), 573-594 (gesamt 22)

Urheber
Dunbar, Zerick Terrell
González-Ochoa, Salvador
Kanagasabai, Thanigaivelan
Ivanova, Alla
Shanker, Anil

DOI
10.1159/000542078
URN
urn:nbn:de:101:1-2412260129022.810468347148
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:34 MESZ

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Beteiligte

  • Dunbar, Zerick Terrell
  • González-Ochoa, Salvador
  • Kanagasabai, Thanigaivelan
  • Ivanova, Alla
  • Shanker, Anil

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