ArticleInternal and emergency medicine2026
Impact of vitamin D plasma levels on in vitro natural killer cell cytotoxicity against non-small cell lung carcinoma in the presence of nivolumab.
Article in Internal and emergency medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Non-small cell lung cancer (NSCLC) continues to be a leading cause of cancer-related death. Although immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have improved patient outcomes, responses vary widely. Natural killer (NK) cells are crucial to antitumor immunity but are often suppressed within the tumor microenvironment. Emerging evidence indicates that vitamin D may influence immune activity, potentially boosting NK cell cytotoxicity and enhancing ICI responses. This study investigated the relationship between PD-L1 expression, NK cell function, and donor vitamin D levels in NSCLC models. Serum vitamin D levels from 63 volunteers were measured by RIA, and NK cells from donors grouped by vitamin D status. NK cytotoxicity was tested using MTT assays on A549 (low PD-L1) and HCC827 (high PD-L1) NSCLC cell lines, with or without PD-1 blockade via nivolumab. Sex-related differences were also analyzed. A significant positive correlation was found between donor vitamin D sufficiency and NK cell cytotoxicity against HCC827 cells, but no such link was observed in A549 cells. This effect was the strongest in male donors with serum vitamin D levels of at least 20 ng/mL, with no additional benefit at higher levels. These findings suggest that maintaining adequate vitamin D levels could enhance NK cell responses to PD-1 inhibitors in NSCLC, especially in tumors with high PD-L1 expression. Overall, the results support exploring vitamin D as an affordable, immune-modulating adjunct to immunotherapy and highlight the importance of personalized, biomarker-guided treatment strategies.
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