Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor-modified T-cell infusions for liver metastases

Cancer Gene Ther. 2014 Nov;21(11):457-62. doi: 10.1038/cgt.2014.50. Epub 2014 Oct 3.


Our phase I Hepatic Immunotherapy for Metastases (HITM) trial tested the safety of chimeric antigen receptor-modified T-cell (CAR-T) hepatic artery infusions (HAI) for unresectable carcinoembryonic antigen (CEA)+ liver metastases (LM). High neutrophil:lymphocyte ratios (NLR) predict poor outcome in cancer patients and we hypothesized that NLR changes would correlate with early responses to CAR-T HAI. Six patients completed the protocol. Three patients received CAR-T HAI in dose escalation (1 × 10(8), 1 × 10(9) and 1 × 10(10) cells) and the remainder received three doses (1 × 10(10) cells) with interleukin (IL)2 support. Serum cytokines and NLR were measured at multiple time points. The mean NLR for all patients was 13.9 (range 4.8-38.1). NLR increased in four patients following treatment with a mean fold change of 1.9. Serum IL6 levels and NLR fold changes demonstrated a trend towards a positive correlation (r=0.77, P=0.10). Patients with poor CEA responses were significantly more likely to have higher NLR level increases (P=0.048). Increased NLR levels were associated with poor responses following CAR-T HAI. NLR variations and associated cytokine changes may be useful surrogates of response to CAR-T HAI.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood
  • Blood Cell Count
  • Cytokines / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Hepatic Artery / metabolism*
  • Humans
  • Immunotherapy / methods*
  • Infusions, Intra-Arterial / methods
  • Interleukin-17 / blood
  • Interleukin-6 / blood
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / secondary*
  • Lymphocytes / cytology
  • Male
  • Middle Aged
  • Neutrophils / cytology
  • Prognosis
  • Receptors, Antigen, T-Cell / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*


  • Biomarkers, Tumor
  • Cytokines
  • Interleukin-17
  • Interleukin-6
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins