Effects of first-line chemotherapy on natural killer cells in adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma

Cancer Chemother Pharmacol. 2016 Jul;78(1):199-207. doi: 10.1007/s00280-016-3070-2. Epub 2016 Jun 11.

Abstract

Purpose: Natural killer (NK) cells are well known to be the most important effector cells mediating antibody-dependent cellular cytotoxicity (ADCC) which is an important mechanism of action of antibody drugs. We evaluated the effects of chemotherapy on the cell number and activity of NK cells from patients who received the vincristine-cyclophosphamide-doxorubicin-prednisone (VCAP), doxorubicin-ranimustine-prednisone (AMP), and vindesine-etoposide-carboplatin-prednisone (VECP) (mLSG15) or mLSG15-like (-L) regimen, which is one of the standard of cares for newly diagnosed adult T-cell leukemia-lymphoma (ATL), or the cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) or CHOP-L regimen which is another standard of care for ATL and peripheral T-cell lymphoma (PTCL).

Methods: The number of lymphocytes and NK cells, and NK cell activity, were assessed using flow cytometry and a (51)Cr release assay, respectively.

Results: A total of 26 patients with untreated ATL or PTCL were enrolled, and blood samples from 25 patients were evaluable. NK cell number in ATL decreased after mLSG15/-L treatment, and the degree of decrease in the NK cell number was more prominent just before VECP therapy (Day 15-17 of each cycle) than just before VCAP therapy (Day 1 of each cycle). The NK cell number in ATL after CHOP/-L treatment also decreased. Interestingly, the NK cell activity showed a tendency to increase after the treatment. NK cell number in PTCL did not decrease by CHOP/-L regimen, but the activity was slightly decreased after the treatment.

Conclusions: These results indicate that the effects of chemotherapeutic agents on NK cells vary according to the disease type and intensity of chemotherapy.

Keywords: ATL; Antibody; Chemotherapy; NK cell; PTCL.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Case-Control Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / administration & dosage
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Etoposide / administration & dosage
  • Female
  • Flow Cytometry
  • Humans
  • Killer Cells, Natural / drug effects*
  • Killer Cells, Natural / metabolism
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Leukemia-Lymphoma, Adult T-Cell / pathology
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / pathology
  • Male
  • Middle Aged
  • Nitrosourea Compounds / administration & dosage
  • Prednisone / administration & dosage
  • Prednisone / pharmacology
  • Prednisone / therapeutic use
  • Vincristine / administration & dosage
  • Vincristine / pharmacology
  • Vincristine / therapeutic use
  • Vindesine / administration & dosage

Substances

  • Nitrosourea Compounds
  • Vincristine
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Carboplatin
  • Vindesine
  • ranimustine
  • Prednisone

Supplementary concepts

  • CHOP protocol