Correspondence

Transplacental Transmission of Natural-Killer-Cell Lymphoma

N Engl J Med 1999; 341:1937December 16, 1999

Article

To the Editor:

In their report of the transfer of an aggressive natural-killer-cell lymphoma from a mother to her fetus, Catlin et al. (July 8 issue)1 suggest that the maternal lymphoma was not rejected by the infant because of the immaturity of the fetus's lymphocytes. We suggest that a fetal antigen called HLA-G is important in protecting maternal cancer cells from rejection by the fetus.

HLA-G is selectively expressed in cytotrophoblasts, chorionic villi, amnion, and monocytes activated by interleukin-10 and interferon-γ.2 It is a key molecule in fetal tolerance of maternal cells.3 In fact, the expression of HLA-G during pregnancy has been shown to protect the semi-allogeneic fetus from rejection by maternal natural killer cells and cytotoxic T lymphocytes.4 Moreover, the expression of HLA-G by malignant cells may permit the escape of the tumor from the patient's immune-surveillance systems.5

High concentrations of soluble HLA-G can be detected in amniotic fluid, which is in continuous exchange with the fetal circulation.2 This soluble HLA-G probably inhibits the lytic activity of the fetus's natural killer cells2 (which are immunologically mature at 33 weeks of gestation), thereby inhibiting rejection of maternal neoplastic cells. We believe that HLA-G plays an important part in the vertical transmission of cancer from mother to fetus.

Edgardo D. Carosella, M.D., Ph.D.
Jean Dausset, M.D., Ph.D.
Nathalie Rouas-Freiss, Pharm.D., Ph.D.
St. Louis Hospital, 75010 Paris, France

5 References

1
Catlin EA, Roberts JD Jr, Erana R, et al. Transplacental transmission of natural-killer-cell lymphoma. N Engl J Med 1999;341:85-91
Full Text | Web of Science | Medline

2
Carosella ED, Rouas-Freiss N, Paul P, Dausset J. HLA-G: a tolerance molecule from the major histocompatibility complex. Immunol Today 1999;20:60-62
CrossRef | Medline

3
Rouas-Freiss N, Khalil-Daher I, Riteau B, et al. The immunotolerance role of HLA-G. Semin Cancer Biol 1999;9:3-12
CrossRef | Web of Science | Medline

4
Rouas-Freiss N, Goncalves RM, Menier C, Dausset J, Carosella ED. Direct evidence to support the role of HLA-G in protecting the fetus from maternal uterine natural killer cytolysis. Proc Natl Acad Sci U S A 1997;94:11520-11525
CrossRef | Web of Science | Medline

5
Paul P, Cabestre FA, Le Gal F-A, et al. Heterogeneity of HLA-G gene transcription and protein expression in malignant melanoma biopsies. Cancer Res 1999;59:1954-1960
Web of Science | Medline

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