title: Neutrophil:lymphocyte ratios and serum cytokine changes after hepatic artery chimeric antigen receptor-modified T-cell infusions for liver metastases.
abstract: 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.
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Saied
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Licata
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Burga
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Thorn
authors.affiliation: Roger Williams Medical Center, Department of Medicine, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: McCormack
authors.affiliation: Roger Williams Medical Center, Department of Radiology, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: B F
authors.initials: BF
authors.lastname: Stainken
authors.affiliation: Roger Williams Medical Center, Department of Radiology, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: E O
authors.initials: EO
authors.lastname: Assanah
authors.affiliation: Roger Williams Medical Center, GMP Core Facility and Clinical Protocol Office, Providence, RI, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Khare
authors.affiliation: Roger Williams Medical Center, GMP Core Facility and Clinical Protocol Office, Providence, RI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Davies
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Espat
authors.affiliation: Roger Williams Medical Center, Department of Medicine, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Junghans
authors.affiliation: Roger Williams Medical Center, Department of Surgery, Providence, RI/Boston University School of Medicine, Boston, MA, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Katz
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001772:Blood Cell Count; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006499:Hepatic Artery / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007261:Infusions, Intra-Arterial / Q000379:methods; D020381:Interleukin-17 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000556:secondary*; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology; D011379:Prognosis; D011948:Receptors, Antigen, T-Cell / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D020381:Interleukin-17; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins