Peripheral blood IFN-gamma-secreting Valpha24+Vbeta11+ NKT cell numbers are decreased in cancer patients independent of tumor type or tumor load.
Natural killer T (NKT) cells are CD1d-restricted lymphoid cells and are characterized by an invariant T-cell receptor, which in humans consists of a Valpha24 chain paired with a Vbeta11 chain. These cells are known for their rapid production of large amounts of cytokines (e.g., IFN-gamma and IL-4), thereby modulating other cells of the immune system such as T cells, NK cells and dendritic cells. NKT cells have been reported to play important regulatory roles in many immune responses, including antitumor immune responses. Here, we demonstrate an age-dependent decrease in circulating Valpha24(+)Vbeta11(+) NKT cell numbers in both healthy controls and cancer patients and demonstrate that in both groups females have higher NKT cell levels compared to males. In a large group of 120 cancer patients, we show that circulating Valpha24(+)Vbeta11(+) NKT cell numbers are about 50% lower than in age- and gender-matched healthy controls and that this decrease is independent of tumor type or tumor load. This decrease was not restored upon tumor removal by means of surgery or radiotherapy. Even though the percentage of NKT cells that secrete IFN-gamma, as detected by ELISPOT, is normal in cancer patients, the absolute number of circulating IFN-gamma-secreting NKT cells is reduced. Together, our results suggest that the reduced circulating Valpha24(+)Vbeta11(+) NKT cell numbers in cancer patients are not affected by tumor load, but might actually reflect a risk factor for tumor development, e.g., by hampering efficient tumor immunosurveillance.
Molling
Johan W
JW
Department of Pathology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Kölgen
Wendy
W
van der Vliet
Hans J J
HJ
Boomsma
Martijn F
MF
Kruizenga
Hinke
H
Smorenburg
Carolien H
CH
Molenkamp
Barbara G
BG
Langendijk
Johannes A
JA
Leemans
C René
CR
von Blomberg
B Mary E
BM
Scheper
Rik J
RJ
van den Eertwegh
Alfons J M
AJ
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001772:Blood Cell Count; D001943:Breast Neoplasms / Q000276:immunology / Q000601:surgery; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000601:surgery; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D012737:Sex Factors; D047368:Tumor Burden
D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma