Docetaxel Upregulates HMGB1 Levels in Non-small Cell Lung Cancer

Biol Pharm Bull. 2020;43(3):399-403. doi: 10.1248/bpb.b19-00702.


Immune checkpoint inhibitors (ICIs) exert beneficial effects in non-small cell lung cancer (NSCLC) patients. However, ICIs are only advantageous for a limited population of NSCLC patients. Therefore to enhance their effects, combination therapies with ICIs have been developed. To identify preferable chemotherapy to combine with ICIs against lung cancer, we examined immunological effects of docetaxel compared with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We found no difference in peripheral lymphocyte counts and ratio of their subpopulations in lung cancer patients before and after both treatments. On the other hand, plasma levels of high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) protein, showed significant increase after docetaxel treatment. Furthermore, we investigated effects of HMGB1 on tumor-infiltrating immune cells obtained from surgically resected tumor tissue from NSCLC patients. When the tumor infiltrating cells were stimulated with HMGB1, CD11c+ cells showed increased expression of activation markers. These findings imply that docetaxel could be involved in anti-tumor immunity via HMGB1. Therefore docetaxel might be a candidate for combination treatment with ICIs.

Keywords: cancer immunotherapy; docetaxel; high-mobility group box 1 (HMGB1); non-small cell lung cancer (NSCLC).

MeSH terms

  • A549 Cells
  • Antineoplastic Agents
  • CD11 Antigens / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Chemokines / metabolism
  • Combined Modality Therapy
  • Cytokines / metabolism
  • Docetaxel / pharmacology*
  • Epidermal Growth Factor / antagonists & inhibitors*
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • HMGB1 Protein / blood
  • HMGB1 Protein / metabolism*
  • Humans
  • Integrin alpha Chains / metabolism
  • Male
  • Mutation
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Transcriptional Activation / drug effects


  • Antineoplastic Agents
  • CD11 Antigens
  • Chemokines
  • Cytokines
  • HMGB1 Protein
  • HMGB1 protein, human
  • ITGAD protein, human
  • Integrin alpha Chains
  • Protein Kinase Inhibitors
  • Docetaxel
  • Epidermal Growth Factor
  • ErbB Receptors
  • Protein-Tyrosine Kinases