Anti-PD-L1 chimeric antigen receptor natural killer cell: Characterization and functional analysis.

Autor: Yazdanpanah-Samani M; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran., Ramezani A; Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran., Sheikhi A; Department of Immunology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran., Mostafavi-Pour Z; Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.; Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran., Erfani N; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Jazyk: angličtina
Zdroj: APMIS : acta pathologica, microbiologica, et immunologica Scandinavica [APMIS] 2024 Dec; Vol. 132 (12), pp. 1115-1127. Date of Electronic Publication: 2024 Oct 28.
DOI: 10.1111/apm.13471
Abstrakt: Like their natural counterparts, chimeric antigen receptor-engineered cells are prone to suppression by inhibitory signals, such as PD-L1, expressed by tumors or suppressor cells in the tumor microenvironment. Consequently, they become impaired, resulting in immune cell exhaustion, tumor progression, and resistance to other therapies. In this study, we developed an anti-PD-L1-CAR NK cell with efficient activity and a notable PD-L1-specific response toward tumor cell lines. The degranulation assay demonstrated that CD107a frequencies between the PD-L1 med and PD-L1 high groups and between Herceptin-treated and non-treated groups were not statistically different. Further investigation into NK cell characterization, considering different markers such as CD57, KIR2D, and CD25, revealed that the majority of the population are activated expanding NK cells. At the same time, immune checkpoint inhibitors, including PD-1, PD-L1, and LAG-3, showed increased levels following activation and expansion. Regarding the efficient functional activity of PD-L1-CAR NK cells and the instinctive receptor balance-based response of NK cells, this observation could point to the inhibition of NK cell overactivation or even higher cytotoxicity and cytokine production rather than exhaustion, especially in the case of healthy NK cells. These findings can contribute to a better understanding of the potential and challenges of using primary NK cells for CAR-NK cell therapy.
(© 2024 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)
Databáze: MEDLINE
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