Abstract 4840: Investigation of the potential immunomodulatory effect of vitamin D supplementation in vitamin D deficient cancer patients

Abstract Background: Advantageous effects of vitamin D supplementation have been studied in certain diseases, but the underlying chromatin remodeling processes remains to be explored in detail during the treatment of cancer patients. Aim: We aimed to assess the molecular effects of high-dose vitamin D supplementation in patients diagnosed with various cancer types. Methods: High-dose (30.000 NE) vitamin D per week was supplemented to 8 patients including 5 lung cancer, 2 colorectal cancer, and 1 urothelial cell carcinomas for two months. Following the blood collection before and after the supplementation period, Histopaque density gradient cell separation was applied to retrieve peripheral mononuclear cells (PBMCs). To examine alterations in the chromatin accessibility after the treatment in PBMCs, assay for transposase-accessible chromatin with sequencing (ATAC-Seq) was performed using the 10X Genomics on a NextSeq 550 instrument with a High Output Sequencing kit (Illumina Inc.). DNA integrity was assessed by the alkaline Comet-assay and telomere qPCR. To analyze further potential epigenetic alterations, global DNA methylation level was estimated on the basis of LINE-1 bisulfite-pyrosequencing experiments on cfDNA and PBMC cells. Results: Vitamin D serum levels elevated 2, 5 fold on average after 2 months of supplementation in all patients. Based on ATAC-Seq, the cellular ratio among PMBC cells altered with an elevated number of NK cells following vitamin D supplementation. DNA integrity was significantly better after treatment in mononuclear cells with decreased Comet assay DNA tail average % (p=0.01), but not in granulocytes. Supplemented samples showed significantly altered telomere length in mononuclear cells (p=0.007). However, no significant difference was observed in cfDNA levels between the sample groups. Slight, but not significant LINE-1 methylation alteration was detected in PBMCs and cfDNA after vitamin D supplementation. Conclusion: Vitamin D supplementation caused significant changes in immune cells that might have an influence on the response to the tumors in cancer patients. Citation Format: Alexandra Kalmar, Zsofia Brigitta Nagy, Liza Dalma Sumegi, Barbara Kinga Bartak, Sandor Spisak, Istvan Takacs, Bela Molnar. Investigation of the potential immunomodulatory effect of vitamin D supplementation in vitamin D deficient cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4840.