SpringerLink
Log in

Vitamin D, autoimmunity and immune-related adverse events of immune checkpoint inhibitors

  • Review
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

In addition to its quintessential role in bone homeostasis, vitamin D also plays an important role in regulating the immune system. As such, many studies have demonstrated the therapeutic benefit of vitamin D in treating autoimmune diseases. This immunomodulatory activity of vitamin D has recently attracted more attention due to the rapid development of immunotherapies for cancers, including melanoma. Patients on cancer immunotherapies can suffer from immune-related adverse events (irAEs), which can involve any organ system and range from common dermatological reactions to extremely severe cases of fatal myocarditis in metastatic melanoma patients. Since there are currently no effective approaches to predict or prevent irAEs, it is attractive to potentially leverage the intriguing immunomodulatory effects of vitamin D within this context. This review will discuss recent research investigating the possibility of using vitamin D to alleviate autoimmunity and irAEs with the hope of improving outcomes for patients on cancer immunotherapies, especially within the context of dermatology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lips P (2006) Vitamin D physiology. Prog Biophys Mol Biol 92:4–8

    CAS  PubMed  Google Scholar 

  2. Norman A (2012) Vitamin D. Elsevier eBook ISBN: 9780323141437. First Published Date: 1st January 1979, Page Count: 508. https://www.elsevier.com/books/vitamin-d/norman/978-0-12-521050-8

  3. Binkley N, Dawson-Hughes B, Durazo-Arvizu R, Thamm M, Tian L, Merkel J, Jones J, Carter G, Sempos C (2017) Vitamin D measurement standardization: the way out of the chaos. J Steroid Biochem Mol Biol 173:117–121

    CAS  PubMed  Google Scholar 

  4. St-Arnaud R (2008) The direct role of vitamin D on bone homeostasis. Arch Biochem Biophys 473:225–230

    CAS  PubMed  Google Scholar 

  5. Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V (2007) Effectiveness and safety of vitamin D in relation to bone health. Evid Rep Technol Assess (Full Rep):1-235. PMID: 18088161. https://pubmed.ncbi.nlm.nih.gov/18088161/

  6. Wang Y, Zhu J, DeLuca HF (2012) Where is the vitamin D receptor? Arch Biochem Biophys 523:123–133

    CAS  PubMed  Google Scholar 

  7. Prietl B, Treiber G, Pieber TR, Amrein K (2013) Vitamin D and immune function. Nutrients 5:2502–2521

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Stucci LS, D'Oronzo S, Tucci M, Macerollo A, Ribero S, Spagnolo F, Marra E, Picasso V, Orgiano L, Marconcini R (2018) Vitamin D in melanoma: controversies and potential role in combination with immune check-point inhibitors. Cancer Treat Rev 69:21–28

    CAS  PubMed  Google Scholar 

  9. Bizzaro G, Antico A, Fortunato A, Bizzaro N (2017) Vitamin D and autoimmune diseases: is vitamin D receptor (VDR) polymorphism the culprit. Isr Med Assoc J 19:438–443

    PubMed  Google Scholar 

  10. Yang C-Y, Leung PS, Adamopoulos IE, Gershwin ME (2013) The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol 45:217–226

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Arnson Y, Amital H, Shoenfeld Y (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 66:1137–1142

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Li J, Chen N, Wang D, Zhang J, Gong X (2018) Efficacy of vitamin D in treatment of inflammatory bowel disease: A meta-analysis. Medicine (Baltimore) 97:e12662. https://doi.org/10.1097/MD.0000000000012662

    Article  CAS  Google Scholar 

  13. Yang L, Weaver V, Smith JP, Bingaman S, Hartman TJ, Cantorna MT (2013) Therapeutic effect of vitamin D supplementation in a pilot study of Crohn’s patients. Clin Transl Gastroenterol 4:e33

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Jørgensen SP, Agnholt J, Glerup H, Lyhne S, Villadsen GE, Hvas C, Bartels L, Kelsen J, Christensen LA, Dahlerup J (2010) Clinical trial: vitamin D3 treatment in Crohn’s disease—a randomized double-blind placebo-controlled study. Aliment Pharmacol Ther 32:377–383

    PubMed  Google Scholar 

  15. Kabbani TA, Koutroubakis IE, Schoen RE, Ramos-Rivers C, Shah N, Swoger J, Regueiro M, Barrie A, Schwartz M, Hashash JG (2016) Association of vitamin D level with clinical status in inflammatory bowel disease: a 5-year longitudinal study. Am J Gastroenterol 111:712

    CAS  PubMed  Google Scholar 

  16. Burton J, Kimball S, Vieth R, Bar-Or A, Dosch H-M, Cheung R, Gagne D, D'souza C, Ursell M, O'connor P (2010) A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 74:1852–1859

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Joshi S, Pantalena L-C, Liu XK, Gaffen SL, Liu H, Rohowsky-Kochan C, Ichiyama K, Yoshimura A, Steinman L, Christakos S (2011) 1, 25-Dihydroxyvitamin D3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol Cell Biol 31:3653–3669

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Herrscher H, Robert C (2020) Immune checkpoint inhibitors in melanoma in the metastatic, neoadjuvant, and adjuvant setting. Curr Opin Oncol 32:106–113

    CAS  PubMed  Google Scholar 

  19. Lebbé C, Meyer N, Mortier L, Marquez-Rodas I, Robert C, Rutkowski P, Menzies AM, Eigentler T, Ascierto PA, Smylie M (2019) Evaluation of two dosing regimens for nivolumab in combination with Ipilimumab in patients with advanced melanoma: results from the phase IIIb/IV CheckMate 511 trial. J Clin Oncol 37:867

    PubMed  PubMed Central  Google Scholar 

  20. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J-J, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R (2019) Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 381:1535–1546

    CAS  PubMed  Google Scholar 

  21. Simeone E, Grimaldi AM, Festino L, Trojaniello C, Vitale MG, Vanella V, Palla M, Ascierto PA (2019) Immunotherapy in metastatic melanoma: a novel scenario of new toxicities and their management. Melanoma Manag 6:MMT30

    PubMed  PubMed Central  Google Scholar 

  22. Hofmann L, Forschner A, Loquai C, Goldinger SM, Zimmer L, Ugurel S, Schmidgen MI, Gutzmer R, Utikal JS, Göppner D (2016) Cutaneous, gastrointestinal, hepatic, endocrine, and renal side-effects of anti-PD-1 therapy. Eur J Cancer 60:190–209

    CAS  PubMed  Google Scholar 

  23. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbe C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J (2017) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377:1345–1356. https://doi.org/10.1056/NEJMoa1709684

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Theofilopoulos AN, Kono DH, Baccala R (2017) The multiple pathways to autoimmunity. Nat Immunol 18:716

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM (1983) Specific high-affinity receptors for 1, 25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 57:1308–1310

    CAS  PubMed  Google Scholar 

  26. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1, 25-dihydroxyvitamin D3 receptors in human leukocytes. Science 221:1181–1183

    CAS  PubMed  Google Scholar 

  27. Zhang Y, Leung DY, Richers BN, Liu Y, Remigio LK, Riches DW, Goleva E (2012) Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol 188:2127–2135

    CAS  PubMed  Google Scholar 

  28. Mattner F, Smiroldo S, Galbiati F, Muller M, Di Lucia P, Poliani PL, Martino G, Panina-Bordignon P, Adorini L (2000) Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1, 25-dihydroxyvitamin D3. Eur J Immunol 30:498–508

    CAS  PubMed  Google Scholar 

  29. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201:233–240. https://doi.org/10.1084/jem.20041257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Harrington LE, Hatton RD, Mangan PR, Turner H, Murphy TL, Murphy KM, Weaver CT (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6:1123–1132. https://doi.org/10.1038/ni1254

    Article  CAS  PubMed  Google Scholar 

  31. Gaffen SL, Jain R, Garg AV, Cua DJ (2014) The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol 14:585

    CAS  PubMed  PubMed Central  Google Scholar 

  32. McGeachy MJ, Cua DJ (2008) Th17 cell differentiation: the long and winding road. Immunity 28:445–453

    CAS  PubMed  Google Scholar 

  33. McGeachy MJ, Cua DJ, Gaffen SL (2019) The IL-17 family of cytokines in health and disease. Immunity 50:892–906

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Chang SH, Chung Y, Dong C (2010) Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression. J Biol Chem 285:38751–38755

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG (2004) Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum: Off J Am Coll Rheumatol 50:72–77

    CAS  Google Scholar 

  36. Kojecky V, Adamikova A, Klimek P (2016) Vitamin D supplementation in inflammatory bowel disease: the role of dosage and patient compliance. Bratisl Lek Listy 117:148–151

    CAS  PubMed  Google Scholar 

  37. Matejuk A (2018) Skin immunity. Arch Immunol Ther Exp 66:45–54

    CAS  Google Scholar 

  38. Scott JF, Das LM, Ahsanuddin S, Qiu Y, Binko AM, Traylor ZP, Debanne SM, Cooper KD, Boxer R, Lu KQ (2017) Oral vitamin D rapidly attenuates inflammation from sunburn: an interventional study. J Invest Dermatol 137:2078–2086

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Das LM, Binko AM, Traylor ZP, Peng H, Lu KQ (2019) Vitamin D improves sunburns by increasing autophagy in M2 macrophages. Autophagy 15:813–826

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Park B-S, Lee D-Y, Youn J-I, Park J-S, Kim I-G (1999) Vitamin D receptor polymorphism is associated with psoriasis. J Invest Dermatol 112:113–116

    CAS  PubMed  Google Scholar 

  41. Richetta AG, Silvestri V, Giancristoforo S, Rizzolo P, D'Epiro S, Graziano V, Mattozzi C, Navazio AS, Campoli M, D'Amico C (2014) A-1012G promoter polymorphism of vitamin D receptor gene is associated with psoriasis risk and lower allele-specific expression. DNA Cell Biol 33:102–109

    CAS  PubMed  Google Scholar 

  42. Zhou X, Xu L-d, Li Y-z (2014) The association of polymorphisms of the vitamin D receptor gene with psoriasis in the Han population of northeastern China. J Dermatol Sci 73:63–66

    CAS  PubMed  Google Scholar 

  43. **e Z, Komuves L, Yu Q-C, Elalieh H, Ng DC, Leary C, Chang S, Crumrine D, Bikle DD, Yoshizawa T (2002) Lack of the vitamin D receptor is associated with reduced epidermal differentiation and hair follicle growth. J Invest Dermatol 118:11–16

    CAS  PubMed  Google Scholar 

  44. Gisondi P, Rossini M, Di Cesare A, Idolazzi L, Farina S, Beltrami G, Peris K, Girolomoni G (2012) Vitamin D status in patients with chronic plaque psoriasis. Br J Dermatol 166:505–510

    CAS  PubMed  Google Scholar 

  45. Ricceri F, Pescitelli L, Tripo L, Prignano F (2013) Deficiency of serum concentration of 25-hydroxyvitamin D correlates with severity of disease in chronic plaque psoriasis. J Am Acad Dermatol 68:511–512

    CAS  PubMed  Google Scholar 

  46. Filoni A, Vestita M, Congedo M, Giudice G, Tafuri S, Bonamonte D (2018) Association between psoriasis and vitamin D: Duration of disease correlates with decreased vitamin D serum levels: An observational case-control study. Medicine (Baltimore) 97:e11185. https://doi.org/10.1097/MD.0000000000011185

    Article  CAS  Google Scholar 

  47. Barrea L, Savanelli MC, Di Somma C, Napolitano M, Megna M, Colao A, Savastano S (2017) Vitamin D and its role in psoriasis: an overview of the dermatologist and nutritionist. Rev Endocr Metab Disord 18:195–205

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Abramovits W (2009) Calcitriol 3 microg/g ointment: an effective and safe addition to the armamentarium in topical psoriasis therapy. J Drugs Dermatol: JDD 8:s17–22

    PubMed  Google Scholar 

  49. Gerritsen M, Van de Kerkhof P, Langner A (2001) Long-term safety of topical calcitriol 3 μg g− 1 ointment. Br J Dermatol 144:17–19

    CAS  PubMed  Google Scholar 

  50. Kircik L (2009) Efficacy and safety of topical calcitriol 3 microg/g ointment, a new topical therapy for chronic plaque psoriasis. J Drugs Dermatol: JDD 8:s9–16

    PubMed  Google Scholar 

  51. Kamangar F, Koo J, Heller M, Lee E, Bhutani T (2013) Oral vitamin D, still a viable treatment option for psoriasis. J Dermatolog Treat 24:261–267

    CAS  PubMed  Google Scholar 

  52. Matsumoto K, Hashimoto K, Nishida Y, Hashiro M, Yoshikawa K (1990) Growth-inhibitory effects of 1, 25-dihydroxyvitamin D3 on normal human keratinocytes cultured in serum-free medium. Biochem Biophys Res Commun 166:916–923

    CAS  PubMed  Google Scholar 

  53. Bikle DD, Oda Y, Teichert A (2011) The vitamin D receptor: a tumor suppressor in skin. Discov Med 11:7

    PubMed  PubMed Central  Google Scholar 

  54. Pollmann R, Solimani F, Schmidt T, Schmidt A, Savai R, Zheng X, Mühlenbein S, Pickert J, Eubel V, Möbs C (2019) Therapeutic targeting of Th17/Tc17 cells leads to clinical improvement of lichen planus. Front Immunol 10:1808

    PubMed  PubMed Central  Google Scholar 

  55. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y (2008) Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 128:2625–2630

    CAS  PubMed  Google Scholar 

  56. Sidbury R, Sullivan A, Thadhani R, Camargo C Jr (2008) Randomized controlled trial of vitamin D supplementation for winter-related atopic dermatitis in Boston: a pilot study. Br J Dermatol 159:245–247

    CAS  PubMed  Google Scholar 

  57. Boutros C, Tarhini A, Routier E, Lambotte O, Ladurie FL, Carbonnel F, Izzeddine H, Marabelle A, Champiat S, Berdelou A (2016) Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat Rev Clin Oncol 13:473–486

    CAS  PubMed  Google Scholar 

  58. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Chen L, Han X (2015) Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Investig 125:3384–3391

    PubMed  PubMed Central  Google Scholar 

  60. Yang JC, Hughes M, Kammula U, Royal R, Sherry RM, Topalian SL, Suri KB, Levy C, Allen T, Mavroukakis S (2007) Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother 30:825 (Hagerstown, Md: 1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Dimitrov V, Bouttier M, Boukhaled G, Salehi-Tabar R, Avramescu RG, Memari B, Hasaj B, Lukacs GL, Krawczyk CM, White JH (2017) Hormonal vitamin D up-regulates tissue-specific PD-L1 and PD-L2 surface glycoprotein expression in humans but not mice. J Biol Chem 292:20657–20668

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Bendix M, Greisen S, Dige A, Hvas CL, Bak N, Jørgensen SP, Dahlerup JF, Deleuran B, Agnholt J (2017) Vitamin D increases programmed death receptor-1 expression in Crohn’s disease. Oncotarget 8:24177

    PubMed  PubMed Central  Google Scholar 

  63. Walunas TL, Lenschow DJ, Bakker CY, Linsley PS, Freeman GJ, Green JM, Thompson CB, Bluestone JA (1994) CTLA-4 can function as a negative regulator of T cell activation. Immunity 1:405–413

    CAS  PubMed  Google Scholar 

  64. Morrison C, Pabla S, Conroy JM, Nesline MK, Glenn ST, Dressman D, Papanicolau-Sengos A, Burgher B, Andreas J, Giamo V (2018) Predicting response to checkpoint inhibitors in melanoma beyond PD-L1 and mutational burden. J Immunother Cancer 6:32

    PubMed  PubMed Central  Google Scholar 

  65. Kaunitz GJ, Cottrell TR, Lilo M, Muthappan V, Esandrio J, Berry S, Xu H, Ogurtsova A, Anders RA, Fischer AH (2017) Melanoma subtypes demonstrate distinct PD-L1 expression profiles. Lab Invest 97:1063–1071

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Ito J, Fujimoto D, Nakamura A, Nagano T, Uehara K, Imai Y, Tomii K (2017) Aprepitant for refractory nivolumab-induced pruritus. Lung Cancer 109:58–61. https://doi.org/10.1016/j.lungcan.2017.04.020

    Article  PubMed  Google Scholar 

  67. Phillips GS, Freites-Martinez A, Wu J, Chan D, Fabbrocini G, Hellmann MD, Lacouture ME (2019) Clinical characterization of immunotherapy-related pruritus among patients seen in 2 oncodermatology clinics. JAMA Dermatol 155:249–251. https://doi.org/10.1001/jamadermatol.2018.4560

    Article  PubMed  Google Scholar 

  68. Collins LK, Chapman MS, Carter JB, Samie FH (2017) Cutaneous adverse effects of the immune checkpoint inhibitors. Curr Probl Cancer 41:125–128. https://doi.org/10.1016/j.currproblcancer.2016.12.001

    Article  PubMed  Google Scholar 

  69. Martins F, Sofiya L, Sykiotis GP, Lamine F, Maillard M, Fraga M, Shabafrouz K, Ribi C, Cairoli A, Guex-Crosier Y, Kuntzer T, Michielin O, Peters S, Coukos G, Spertini F, Thompson JA, Obeid M (2019) Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol 16:563–580. https://doi.org/10.1038/s41571-019-0218-0

    Article  CAS  PubMed  Google Scholar 

  70. Saibil SD, Bonilla L, Majeed H, Sotov V, Hogg D, Chappell MA, Cybulsky M, Butler MO (2019) Fatal myocarditis and rhabdomyositis in a patient with stage IV melanoma treated with combined ipilimumab and nivolumab. Curr Oncol 26:e418–e421. https://doi.org/10.3747/co.26.4381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Coleman E, Ko C, Dai F, Tomayko MM, Kluger H, Leventhal JS (2019) Inflammatory eruptions associated with immune checkpoint inhibitor therapy: a single-institution retrospective analysis with stratification of reactions by toxicity and implications for management. J Am Acad Dermatol 80:990–997

    CAS  PubMed  Google Scholar 

  72. Postow MA, Sidlow R, Hellmann MD (2018) Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 378:158–168

    CAS  PubMed  Google Scholar 

  73. Trinh S, Le A, Gowani S, La-Beck NM (2019) Management of immune-related adverse events associated with immune checkpoint inhibitor therapy: a minireview of current clinical guidelines. Asia-Pac J Oncol Nurs 6:154

    PubMed  PubMed Central  Google Scholar 

  74. Liudahl SM, Coussens LM (2018) B cells as biomarkers: predicting immune checkpoint therapy adverse events. J Clin Invest 128:577–579. https://doi.org/10.1172/JCI99036

    Article  PubMed  PubMed Central  Google Scholar 

  75. Puzanov I, Diab A, Abdallah K, Bingham C, Brogdon C, Dadu R, Hamad L, Kim S, Lacouture M, LeBoeuf N (2017) Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the society for immunotherapy of cancer (SITC) Toxicity management working group. J Immunother Cancer 5:95

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Balak DM, Hajdarbegovic E (2017) Drug-induced psoriasis: clinical perspectives. Psoriasis (Auckland, NZ) 7:87

    CAS  Google Scholar 

  77. Deeb KK, Trump DL, Johnson CS (2007) Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat Rev Cancer 7:684–700

    CAS  PubMed  Google Scholar 

  78. Tarhini AA, Zahoor H, Lin Y, Malhotra U, Sander C, Butterfield LH, Kirkwood JM (2015) Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma. J Immunother Cancer 3:39

    PubMed  PubMed Central  Google Scholar 

  79. Bamias G, Delladetsima I, Perdiki M, Siakavellas SI, Goukos D, Papatheodoridis GV, Daikos GL, Gogas H (2017) Immunological characteristics of colitis associated with anti-CTLA-4 antibody therapy. Cancer Invest 35:443–455

    CAS  PubMed  Google Scholar 

  80. Das R, Bar N, Ferreira M, Newman AM, Zhang L, Bailur JK, Bacchiocchi A, Kluger H, Wei W, Halaban R (2018) Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Investig 128:715–720

    PubMed  PubMed Central  Google Scholar 

  81. Shahabi V, Berman D, Chasalow SD, Wang L, Tsuchihashi Z, Hu B, Panting L, Jure-Kunkel M, Ji R-R (2013) Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. J Transl Med 11:75

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Donaldson M, Owen JL, Chae YK, Choi JN (2018) Management of persistent pruritus and lichenoid reaction secondary to nivolumab with narrowband ultraviolet B phototherapy. Front Oncol 8:405

    PubMed  PubMed Central  Google Scholar 

  83. Rácz E, Prens EP, Kurek D, Kant M, De Ridder D, Mourits S, Baerveldt EM, Ozgur Z, Van Ijcken WF, Laman JD (2011) Effective treatment of psoriasis with narrow-band UVB phototherapy is linked to suppression of the IFN and Th17 pathways. J Invest Dermatol 131:1547–1558

    PubMed  Google Scholar 

  84. Mason AR, Mason J, Cork M, Dooley G, Hancock H (2013) Topical treatments for chronic plaque psoriasis. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD005028.pub3

    Article  PubMed  Google Scholar 

  85. Dankers W, Colin EM, van Hamburg JP, Lubberts E (2017) Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential. Front Immunol 7:697

    PubMed  PubMed Central  Google Scholar 

  86. Dankers W, Davelaar N, Van Hamburg JP, van de Peppel J, Colin EM, Lubberts E (2019) Human memory Th17 cell populations change into anti-inflammatory cells with regulatory capacity upon exposure to active vitamin D. Front Immunol 10:1504

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Hitchon CA, Sun Y, Robinson DB, Peschken CA, Bernstein CN, Siminovitch KA, El-Gabalawy HS (2012) Vitamin D receptor polymorphism rs2228570 (Fok1) is associated with rheumatoid arthritis in North American natives. J Rheumatol 39:1792–1797

    CAS  PubMed  Google Scholar 

  88. Karray EF, Dhifallah IB, Abdelghani KB, Ghorbel IB, Khanfir M, Houman H, Hamzaoui K, Zakraoui L (2012) Associations of vitamin D receptor gene polymorphisms FokI and BsmI with susceptibility to rheumatoid arthritis and Behçet’s disease in Tunisians. Joint Bone Spine 79:144–148

    CAS  PubMed  Google Scholar 

  89. Mosaad YM, Hammad EM, Fawzy Z, Aal IAA, Youssef HM, ElSaid TO, Monir R, EL-Deek BS (2014) Vitamin D receptor gene polymorphism as possible risk factor in rheumatoid arthritis and rheumatoid related osteoporosis. Hum Immunol 75:452–461

    CAS  PubMed  Google Scholar 

  90. Cox MB, Ban M, Bowden NA, Baker A, Scott RJ, Lechner-Scott J (2012) Potential association of vitamin D receptor polymorphism Taq1 with multiple sclerosis. Mult Scler J 18:16–22

    CAS  Google Scholar 

  91. Tajouri L, Ovcaric M, Curtain R, Johnson MP, Griffiths LR, Csurhes P, Pender MP, Lea RA (2005) Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population. J Neurogenet 19:25–38

    CAS  PubMed  Google Scholar 

  92. Niino M, Fukazawa T, Yabe I, Kikuchi S, Sasaki H, Tashiro K (2000) Vitamin D receptor gene polymorphism in multiple sclerosis and the association with HLA class II alleles. J Neurol Sci 177:65–71

    CAS  PubMed  Google Scholar 

  93. Panierakis C, Goulielmos G, Mamoulakis D, Petraki E, Papavasiliou E, Galanakis E (2009) Vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Crete, Greece. Clin Immunol 133:276–281

    CAS  PubMed  Google Scholar 

  94. Taverna M, Sola A, Guyot-Argenton C, Pacher N, Bruzzo F, Slama G, Reach G, Selam J-L (2002) Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy. Diabetologia 45:436–442

    CAS  PubMed  Google Scholar 

  95. Rasoul MA, Haider MZ, Al-Mahdi M, Al-Kandari H, Dhaunsi GS (2019) Relationship of four vitamin D receptor gene polymorphisms with type 1 diabetes mellitus susceptibility in Kuwaiti children. BMC Pediatr 19:71

    PubMed  PubMed Central  Google Scholar 

  96. Luo X, Yang M, Wu F, Wu L, Chen L, Tang Z, Liu N, Zeng X, Guan J, Yuan G (2012) Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population. Lupus 21:53–59

    CAS  PubMed  Google Scholar 

  97. Ozaki Y, Nomura S, Nagahama M, Yoshimura C, Kagawa H, Fukuhara S (2000) Vitamin-D receptor genotype and renal disorder in Japanese patients with systemic lupus erythematosus. Nephron 85:86–91

    CAS  PubMed  Google Scholar 

  98. Carvalho C, Marinho A, Leal B, Bettencourt A, Boleixa D, Almeida I, Farinha F, Costa P, Vasconcelos C, Silva B (2015) Association between vitamin D receptor (VDR) gene polymorphisms and systemic lupus erythematosus in Portuguese patients. Lupus 24:846–853

    CAS  PubMed  Google Scholar 

  99. Zaltman C, Soares-Mota M (2017) P-311 vitamin D receptor gene polymorphisms, serum vitamin D and poor predictor prognosis in IBD patients. Inflamm Bowel Dis. https://doi.org/10.1097/01.MIB.0000512852.89032.49

    Article  Google Scholar 

  100. Wang L, Wang Z, Hu J, Fan R, Zhou J, Zhong J (2014) Polymorphisms of the vitamin D receptor gene and the risk of inflammatory bowel disease: a meta-analysis. Genet Mol Res 13:2598–2610

    CAS  PubMed  Google Scholar 

  101. Naderi N, Farnood A, Habibi M, Derakhshan F, Balaii H, Motahari Z, Agah MR, Firouzi F, Rad MG, Aghazadeh R, Zojaji H, Zali MR (2008) Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 23:1816–1822. https://doi.org/10.1111/j.1440-1746.2008.05525.x

    Article  CAS  PubMed  Google Scholar 

  102. Lin J, Liu J, Davies ML, Chen W (2016) Serum vitamin D level and rheumatoid arthritis disease activity: review and meta-analysis. PloS One 11

  103. Lee YH, Bae SC (2016) Vitamin D level in rheumatoid arthritis and its correlation with the disease activity: a meta-analysis. Clin Exp Rheumatol 34:827–833

    PubMed  Google Scholar 

  104. Azzeh FS, Kensara OA (2015) Vitamin D is a good marker for disease activity of rheumatoid arthritis disease. Dis Markers 2015:260725. https://doi.org/10.1155/2015/260725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna J, Lilius E, Mononen I (2008) A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 79:152–157

    PubMed  Google Scholar 

  106. Ascherio A, Munger KL, White R, Köchert K, Simon KC, Polman CH, Freedman MS, Hartung H-P, Miller DH, Montalbán X (2014) Vitamin D as an early predictor of multiple sclerosis activity and progression. JAMA Neurol 71:306–314

    PubMed  PubMed Central  Google Scholar 

  107. Mokry LE, Ross S, Ahmad OS, Forgetta V, Smith GD, Goltzman D, Leong A, Greenwood CM, Thanassoulis G, Richards JB (2015) Vitamin D and risk of multiple sclerosis: a mendelian randomization study. PLoS Med 12:e1001866. https://doi.org/10.1371/journal.pmed.1001866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. De Boer IH, Sachs MC, Cleary PA, Hoofnagle AN, Lachin JM, Molitch ME, Steffes MW, Sun W, Zinman B, Brunzell JD (2012) Circulating vitamin D metabolites and kidney disease in type 1 diabetes. J Clin Endocrinol Metab 97:4780–4788

    PubMed  PubMed Central  Google Scholar 

  109. Singh DK, Winocour P, Summerhayes B, Viljoen A, Sivakumar G, Farrington K (2009) Are low erythropoietin and 1, 25-dihydroxyvitamin D levels indicative of tubulo-interstitial dysfunction in diabetes without persistent microalbuminuria? Diabetes Res Clin Pract 85:258–264

    CAS  PubMed  Google Scholar 

  110. Ismail MM, Hamid TAA, Ibrahim AA, Marzouk H (2017) Serum adipokines and vitamin D levels in patients with type 1 diabetes mellitus. Arch Med Sci: AMS 13:738

    CAS  PubMed  Google Scholar 

  111. Shen L, Zhuang QS, Ji HF (2016) Assessment of vitamin D levels in type 1 and type 2 diabetes patients: results from metaanalysis. Mol Nutr Food Res 60:1059–1067

    CAS  PubMed  Google Scholar 

  112. Sumethkul K, Boonyaratavej S, Kitumnuaypong T, Angthararuk S, Cheewasat P, Manadee N, Sumethkul V (2013) The predictive factors of low serum 25-hydroxyvitamin D and vitamin D deficiency in patients with systemic lupus erythematosus. Rheumatol Int 33:1461–1467

    CAS  PubMed  Google Scholar 

  113. Schoindre Y, Jallouli M, Tanguy M-L, Ghillani P, Galicier L, Aumaître O, Francès C, Le Guern V, Lioté F, Smail A (2014) Lower vitamin D levels are associated with higher systemic lupus erythematosus activity, but not predictive of disease flare-up. Lupus Sci Med 1:e000027

    PubMed  PubMed Central  Google Scholar 

  114. Young KA, Munroe ME, Guthridge JM, Kamen DL, Niewold TB, Gilkeson GS, Weisman MH, Ishimori ML, Kelly J, Gaffney PM (2017) Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus. Ann Rheum Dis 76:153–158

    CAS  PubMed  Google Scholar 

  115. Zammit SC, Ellul P, Girardin G, Valpiani D, Nielsen KR, Olsen J, Goldis A, Lazar D, Shonová O, Nováková M (2018) Vitamin D deficiency in a European inflammatory bowel disease inception cohort: an Epi-IBD study. Eur J Gastroenterol Hepatol 30:1297–1303

    Google Scholar 

  116. Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG, Issa M (2011) Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr 35:308–316. https://doi.org/10.1177/0148607110381267

    Article  CAS  PubMed  Google Scholar 

  117. Joseph RW, Cappel M, Goedjen B, Gordon M, Kirsch B, Gilstrap C, Bagaria S, Jambusaria-Pahlajani A (2015) Lichenoid dermatitis in three patients with metastatic melanoma treated with anti-PD-1 therapy. Cancer Immunol Res 3:18–22. https://doi.org/10.1158/2326-6066.CIR-14-0134

    Article  PubMed  Google Scholar 

  118. Shi VJ, Rodic N, Gettinger S, Leventhal JS, Neckman JP, Girardi M, Bosenberg M, Choi JN (2016) Clinical and histologic features of lichenoid mucocutaneous eruptions due to anti-programmed cell death 1 and anti-programmed cell death ligand 1 immunotherapy. JAMA Dermatol 152:1128–1136. https://doi.org/10.1001/jamadermatol.2016.2226

    Article  PubMed  PubMed Central  Google Scholar 

  119. McDermott DF, Sosman JA, Sznol M, Massard C, Gordon MS, Hamid O, Powderly JD, Infante JR, Fasso M, Wang YV, Zou W, Hegde PS, Fine GD, Powles T (2016) Atezolizumab, an anti-programmed death-ligand 1 antibody, in metastatic renal cell carcinoma: long-term safety, clinical activity, and immune correlates from a phase Ia study. J Clin Oncol 34:833–842. https://doi.org/10.1200/JCO.2015.63.7421

    Article  CAS  PubMed  Google Scholar 

  120. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB (2012) Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med 366:2443–2454

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob J-J, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF (2017) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377:1345–1356

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, Khushalani NI, Lewis K, Lao CD, Postow MA (2018) Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med 379:722–730

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382:810–821

    CAS  PubMed  Google Scholar 

  124. Jaber SH, Cowen EW, Haworth LR, Booher SL, Berman DM, Rosenberg SA, Hwang ST (2006) Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent. Arch Dermatol 142:166–172. https://doi.org/10.1001/archderm.142.2.166

    Article  CAS  PubMed  Google Scholar 

  125. Hwang SJ, Carlos G, Wakade D, Byth K, Kong BY, Chou S, Carlino MS, Kefford R, Fernandez-Penas P (2016) Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: a single-institution cohort. J Am Acad Dermatol 74(455–461):e451. https://doi.org/10.1016/j.jaad.2015.10.029

    Article  Google Scholar 

  126. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Brahmer JR, Tykodi SS, Chow LQ, Hwu W-J, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K (2012) Safety and activity of anti–PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Rosenberg JE, Hoffman-Censits J, Powles T, Van Der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Bonigen J, Raynaud-Donzel C, Hureaux J, Kramkimel N, Blom A, Jeudy G, Breton AL, Hubiche T, Bedane C, Legoupil D (2017) Anti-PD 1-induced psoriasis: a study of 21 patients. J Eur Acad Dermatol Venereol 31:e254–e257

    CAS  PubMed  Google Scholar 

  130. Kato Y, Otsuka A, Miyachi Y, Kabashima K (2016) Exacerbation of psoriasis vulgaris during nivolumab for oral mucosal melanoma. J Eur Acad Dermatol Venereol 30:e89–e91. https://doi.org/10.1111/jdv.13336

    Article  CAS  PubMed  Google Scholar 

  131. Collins M, Michot J, Danlos F, Mussini C, Soularue E, Mateus C, Loirat D, Buisson A, Rosa I, Lambotte O (2017) Inflammatory gastrointestinal diseases associated with PD-1 blockade antibodies. Ann Oncol 28:2860–2865

    CAS  PubMed  Google Scholar 

  132. Baroudjian B, Lourenco N, Chami I, Maillet M, Bertheau P, Bagot M, Gornet J-M, Lebbé C, Allez M (2016) Anti-PD1-induced collagenous colitis in a melanoma patient. Melanoma Res 26:308–311

    CAS  PubMed  Google Scholar 

  133. Marthey L, Mateus C, Mussini C, Nachury M, Nancey S, Grange F, Zallot C, Peyrin-Biroulet L, Rahier JF, Bourdier de Beauregard M, Mortier L, Coutzac C, Soularue E, Lanoy E, Kapel N, Planchard D, Chaput N, Robert C, Carbonnel F (2016) Cancer Immunotherapy with Anti-CTLA-4 Monoclonal Antibodies Induces an Inflammatory Bowel Disease. J Crohns Colitis 10:395–401. https://doi.org/10.1093/ecco-jcc/jjv227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Gonzalez-Cao M, Boada A, Teixido C, Fernandez-Figueras MT, Mayo C, Tresserra F, Bustamante J, Viteri S, Puertas E, Santarpia M, Riso A, Barron F, Karachaliou N, Rosell R (2016) Fatal gastrointestinal toxicity with ipilimumab after BRAF/MEK inhibitor combination in a melanoma patient achieving pathological complete response. Oncotarget 7:56619–56627. https://doi.org/10.18632/oncotarget.10651

    Article  PubMed  PubMed Central  Google Scholar 

  135. Beck KE, Blansfield JA, Tran KQ, Feldman AL, Hughes MS, Royal RE, Kammula US, Topalian SL, Sherry RM, Kleiner D, Quezado M, Lowy I, Yellin M, Rosenberg SA, Yang JC (2006) Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol 24:2283–2289. https://doi.org/10.1200/JCO.2005.04.5716

    Article  CAS  PubMed  Google Scholar 

  136. Berman D, Parker SM, Siegel J, Chasalow SD, Weber J, Galbraith S, Targan SR, Wang HL (2010) Blockade of cytotoxic T-lymphocyte antigen-4 by ipilimumab results in dysregulation of gastrointestinal immunity in patients with advanced melanoma. Cancer Immun 10:11

    PubMed  PubMed Central  Google Scholar 

  137. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im S-A, Shaw Wright G (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121

    CAS  PubMed  Google Scholar 

  138. De Martin E, Michot J-M, Papouin B, Champiat S, Mateus C, Lambotte O, Roche B, Antonini TM, Coilly A, Laghouati S (2018) Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol 68:1181–1190

    PubMed  Google Scholar 

  139. Hsu P-C, Li S-H, Yang C-T (2018) Recurrent pneumonitis induced by atezolizumab (anti–programmed death ligand 1) in nsclc patients who previously experienced anti-programmed death 1 immunotherapy-related pneumonitis. J Thoracic Oncol 13:e227–e230

    Google Scholar 

  140. Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, Rathmell WK, Ancell KK, Balko JM, Bowman C, Davis EJ, Chism DD, Horn L, Long GV, Carlino MS, Lebrun-Vignes B, Eroglu Z, Hassel JC, Menzies AM, Sosman JA, Sullivan RJ, Moslehi JJ, Johnson DB (2018) Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol 4:1721–1728. https://doi.org/10.1001/jamaoncol.2018.3923

    Article  PubMed  PubMed Central  Google Scholar 

  141. Salem JE, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, Gobert A, Spano JP, Balko JM, Bonaca MP, Roden DM, Johnson DB, Moslehi JJ (2018) Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol 19:1579–1589. https://doi.org/10.1016/S1470-2045(18)30608-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Blansfield JA, Beck KE, Tran K, Yang JC, Hughes MS, Kammula US, Royal RE, Topalian SL, Haworth LR, Levy C (2005) Cytotoxic T-lymphocyte–associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother 28:593 (Hagerstown, Md: 1997)

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, Waterfield W, Schadendorf D, Smylie M, Guthrie T Jr (2010) Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol 11:155–164

    CAS  PubMed  Google Scholar 

  144. O'day S, Maio M, Chiarion-Sileni V, Gajewski T, Pehamberger H, Bondarenko I, Queirolo P, Lundgren L, Mikhailov S, Roman L (2010) Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol 21:1712–1717

    CAS  PubMed  Google Scholar 

  145. Weber J, Thompson JA, Hamid O, Minor D, Amin A, Ron I, Ridolfi R, Assi H, Maraveyas A, Berman D (2009) A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clin Cancer Res 15:5591–5598

    CAS  PubMed  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, OH, USA

    Lillian Sun

  2. Department of Dermatology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    Joshua Arbesman & Melissa Piliang

Authors
  1. Lillian Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joshua Arbesman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melissa Piliang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the concepts of the review, and the writing and editing phases of the review.

Corresponding author

Correspondence to Melissa Piliang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, L., Arbesman, J. & Piliang, M. Vitamin D, autoimmunity and immune-related adverse events of immune checkpoint inhibitors. Arch Dermatol Res 313, 1–10 (2021). https://doi.org/10.1007/s00403-020-02094-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-020-02094-x

Keywords

Search

Navigation