A novel method to quantify and characterize leukemia-reactive natural killer cells in patients undergoing allogeneic hematopoietic stem cell transplantation following conventional or reduced-dose conditioning.
The antitumor activity of natural killer (NK) cells has recently been shown to be assessable at a single-cell level via flow cytometric detection of CD107a. We used this novel method to prospectively quantify and characterize tumor-reactive NK cells in patients undergoing myeloablative or nonmyeloablative conditioning and allogeneic hematopoietic stem cell transplantation (HSCT). Degranulation of NK cells in the peripheral blood of 34 patients after HSCT (day +30, day +90) was determined by evaluating CD107a expression after coincubation of the cells with tumor targets. The percentage of degranulating NK cells was higher after nonmyeloablative conditioning than after myeloablative conditioning (P<.001), indicating a higher activation state and increased antitumor activity of NK cells after nonmyeloablative conditioning. We were able to analyze NK cell subsets separately and found that CD56bright NK cells following HSCT are functionally different from CD56bright NK cells in healthy donors, as indicated by a high percentage of degranulating NK cells in response to tumor targets in patients after HSCT. The CD107a assay is a new and feasible method to quantify and characterize tumor-reactive NK cells after HSCT. Using this method, we found that NK cells had high antitumor cytotoxic activity after nonmyeloablative conditioning, which may contribute to the effectiveness of nonmyeloablative conditioning.
Penack
Olaf
O
Department of Hematology, Charité, Campus Benjamin Franklin, Berlin, Germany. olaf.penack@charite.de
Fischer
Lars
L
Stroux
Andrea
A
Gentilini
Chiara
C
Nogai
Axel
A
Muessig
Arne
A
Ganepola
Susanne
S
Lange
Thoralf
T
Kliem
Constanze
C
Marinets
Olga
O
Blau
Igor Wolfgang
IW
Thiel
Eckhard
E
Uhareka
Lutz
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D019002:CD56 Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D019337:Hematologic Neoplasms / Q000276:immunology* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D019002:CD56 Antigen; D052118:Lysosomal-Associated Membrane Protein 1