Vitamin D and Immune Checkpoint Inhibitors in Lung Cancer: A Synergistic Approach to Enhancing Treatment Efficacy

Int J Mol Sci. 2025 May 9;26(10):4511. doi: 10.3390/ijms26104511.

Abstract

Lung cancer, a malignant neoplasm that is globally prevalent and characterized by high incidence and mortality rates, has seen the rise of immune checkpoint inhibitors (ICIs) as a crucial systemic treatment. However, a subset of patients exhibits suboptimal responses to ICIs. Recently, studies revealed the role of vitamin D in inflammation modulation, cell differentiation, and cancer prevention. Vitamin D precisely modulates immune responses and inflammatory states within the tumor microenvironment (TME) by targeting both innate and adaptive immunity. These effects may reduce immune tolerance to ICIs and synergistically enhance their therapeutic efficacy. Here, we review vitamin D metabolism in lung cancer patients, as well as its anti-tumor mechanisms, immune regulation, and the significant promise of vitamin D in lung cancer immunotherapy and adjuvant therapeutic strategies. Further research is imperative to surmount these challenges and fully realize vitamin D's potential in improving lung cancer immunotherapy outcomes.

Keywords: immune checkpoint inhibitors; lung cancer; synergistic effect; vitamin D.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors* / pharmacology
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy / methods
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / metabolism
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology
  • Vitamin D* / metabolism
  • Vitamin D* / pharmacology
  • Vitamin D* / therapeutic use

Substances

  • Immune Checkpoint Inhibitors
  • Vitamin D