Vitamin D in melanoma: Controversies and potential role in combination with immune check-point inhibitors

L.S. Stucci, S. D'Oronzo, M. Tucci, A. Macerollo, S. Ribero, F. Spagnolo, E. Marra, V. Picasso, L. Orgiano, R. Marconcini, F. De Rosa, L.D. Guardo, G. Galli, S. Gandini, R. Palmirotta, G. Palmieri, P. Queirolo, F. Silvestris, for the Italian Melanoma Intergroup (IMI)

Research output: Contribution to journalArticlepeer-review


The role of vitamin D in melanoma is still controversial. Although several Authors described a correlation between vitamin D deficiency and poor survival in metastatic melanoma patients, clinical trials exploring the effects of vitamin D supplementation in this clinical setting were mostly inconclusive. However, recent evidence suggests that vitamin D exerts both anti-proliferative effects on tumor cells and immune-modulating activities, that have been widely explored in auto-immune disorders. On the one hand, vitamin D has been shown to inhibit T-helper17 lymphocytes, notoriously involved in the pathogenesis of immune-related adverse events (iAEs) which complicate immune-checkpoint inhibitor (ICI) treatment. On the other hand, vitamin D up-regulates PDL-1 expression on both epithelial and immune cells, suggesting a synergic effect in combination with ICIs, for which further investigation is needed. © 2018 Elsevier Ltd
Original languageEnglish
Pages (from-to)21-28
Number of pages8
JournalCancer Treatment Reviews
Publication statusPublished - 2018


  • Immune check-point inhibitors
  • Immune related adverse events
  • Melanoma
  • PDL-1
  • Vitamin D
  • beta3 integrin
  • calcitriol
  • calcium
  • cathelicidin
  • checkpoint kinase inhibitor
  • colecalciferol
  • cyclin dependent kinase inhibitor 1
  • cyclin dependent kinase inhibitor 1B
  • ergocalciferol
  • glucocorticoid
  • infliximab
  • interleukin 12
  • interleukin 17
  • ipilimumab
  • mitogen activated protein kinase
  • nivolumab
  • osteoclast differentiation factor
  • osteopontin
  • oxygenase
  • phosphatidylinositol 3 kinase
  • placebo
  • protein kinase B
  • S100 calcium binding protein G
  • somatomedin binding protein
  • vitamin D
  • vitamin D receptor
  • CD274 protein, human
  • cytotoxic T lymphocyte antigen 4
  • monoclonal antibody
  • programmed death 1 ligand 1
  • adaptive immunity
  • antineoplastic activity
  • antiproliferative activity
  • apoptosis
  • calcium absorption
  • cancer survival
  • cell cycle progression
  • cell differentiation
  • cell proliferation
  • colitis
  • conformational transition
  • diarrhea
  • down regulation
  • drug absorption
  • drug receptor binding
  • drug structure
  • epithelium cell
  • helper cell
  • human
  • hypertransaminasemia
  • immunocompetent cell
  • immunomodulation
  • immunoregulation
  • innate immunity
  • loading drug dose
  • melanoma
  • overall survival
  • progression free survival
  • protein cleavage
  • protein expression
  • protein function
  • Review
  • Th17 cell
  • tumor microenvironment
  • ultraviolet radiation
  • upregulation
  • vitamin D deficiency
  • vitamin supplementation
  • antagonists and inhibitors
  • combination drug therapy
  • prognosis
  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CTLA-4 Antigen
  • Drug Therapy, Combination
  • Humans
  • Prognosis


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