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Consequently, they become impaired, resulting in immune cell exhaustion, tumor progression, and resistance to other therapies. In this study, we developed an anti\u2010PD\u2010L1\u2010CAR NK cell with efficient activity and a notable PD\u2010L1\u2010specific response toward tumor cell lines. The degranulation assay demonstrated that CD107a frequencies between the PD\u2010L1<jats:sup>med<\/jats:sup> and PD\u2010L1<jats:sup>high<\/jats:sup> groups and between Herceptin\u2010treated and non\u2010treated 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\u20101, PD\u2010L1, and LAG\u20103, showed increased levels following activation and expansion. Regarding the efficient functional activity of PD\u2010L1\u2010CAR NK cells and the instinctive receptor balance\u2010based 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\u2010NK cell therapy.<\/jats:p>","DOI":"10.1111\/apm.13471","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T18:22:35Z","timestamp":1730139755000},"page":"1115-1127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Anti\u2010<scp>PD<\/scp>\u2010<scp>L1<\/scp> chimeric antigen receptor natural killer cell: Characterization and functional analysis"],"prefix":"10.1111","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8140-380X","authenticated-orcid":false,"given":"Mahsa","family":"Yazdanpanah\u2010Samani","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences  Shiraz 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