T-cell analysis in identical twins reveals an impaired anti-follicular lymphoma immune response in the patient but not in the healthy twin.
In lymphomas an innate defect in the T-cell repertoire could account for the impaired tumour-specific immune response; alternatively, the tumour itself could exert an inhibitory effect on the immune system. To address this issue we analysed the T-cell responses against follicular lymphoma (FL) in identical twins as it can be postulated that their overall T-cell repertoire is identical. While differences between the T-cell response of the patient and the healthy twin would point to a tumour-induced T-cell unresponsiveness, impaired responses in both would point to a defective T-cell repertoire. We demonstrated an impaired tumour-specific proliferation (P = 0.035 and P = 0.013) and cytokine release (P = 0.004 and P = 0.0008) of both peripheral blood and tumour-derived T-cells, respectively, in the FL patient compared with the T-cell response of the healthy twin. Moreover, only syngeneic primed T cells were able to directly lyse unmodified FL cells of the patient. These data support previous findings in murine lymphomas and suggest that inhibitory mechanisms during tumour growth, rather than a defective T-cell repertoire, are responsible for the insufficient T-cell response in lymphoma.
Gitelson
Elena
E
Advanced Therapeutics Program, Sunnybrook and Women's College Health Sciences Centre, Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada.
Spaner
David
D
Buckstein
Rena
R
Franssen
Edmee
E
Hewitt
Karen
K
Lim
Megan S
MS
Pennell
Nancy
N
Schultze
Joachim L
JL
Berinstein
Neil L
NL
D000328:Adult; D002455:Cell Division; D003601:Cytotoxicity Tests, Immunologic; D004200:Diseases in Twins; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008224:Lymphoma, Follicular / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014430:Twins, Monozygotic
D007371:Interferon-gamma