Frontiers in Immunology (Sep 2022)

Vitamin D metabolism pathway polymorphisms are associated with efficacy and safety in patients under anti-PD-1 inhibitor therapy

  • Jianquan Luo,
  • Jianquan Luo,
  • Huiqing Chen,
  • Huiqing Chen,
  • Fang Ma,
  • Chenlin Xiao,
  • Chenlin Xiao,
  • Bao Sun,
  • Bao Sun,
  • Yiping Liu,
  • Yiping Liu,
  • Haoneng Tang,
  • Haoneng Tang,
  • Yue Yang,
  • Wenhui Liu,
  • Wenhui Liu,
  • Zhiying Luo,
  • Zhiying Luo

DOI
https://doi.org/10.3389/fimmu.2022.937476
Journal volume & issue
Vol. 13

Abstract

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AimVitamin D (VitD) signaling has been increasingly investigated for its role in stimulating the innate and adaptive immune systems and suppressing inflammatory responses. Therefore, we examined the associations between VitD-related genetic polymorphisms, plasma 25-hydroxyvitamin D (25(OH)D), and the efficacy and safety of immune checkpoint inhibitors (ICIs).Patients and methodsA total of 13 single-nucleotide polymorphisms (SNPs) in VitD metabolic pathway genes were genotyped in 343 cancer patients receiving ICI treatment using the MassARRAY platform. In 65 patients, the associations between plasma 25(OH)D levels and ICI treatment outcomes were investigated further.ResultsWe found that the CYP24A1 rs6068816TT and rs2296241AA genotypes were significantly higher in patients who responded to ICIs. Furthermore, patients with higher plasma 25(OH)D levels had a better treatment response. The distribution of allele and genotype frequencies showed that three SNPs (rs10877012, rs2762934, and rs8018720) differed significantly between patients who had immune-related adverse events (irAEs) and those who did not. There was no statistically significant relationship between plasma 25(OH)D levels and the risk of irAEs.ConclusionIn summary, our findings showed that genetic variations in the VitD metabolism pathway were associated with ICI treatment outcomes, and VitD supplementation may be useful in improving ICI treatment efficacy.

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