Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: Impaired NK cell development and recruitment

Mice deficient in lymphotoxin (LT)-alpha lack peripheral lymph nodes and Peyer's patches and have profound defects in development of follicular dendritic cell networks, germinal center formation, and T/B cell segregation in the spleen. Although LT alpha is known to be expressed by NK cells as well as T and B lymphocytes, the requirement of LT alpha for NK cell functions is largely unknown. To address this issue, we have assessed NK cell functions in LT alpha-deficient mice by evaluating tumor models with known requirements for NK cells to control their growth and metastasis, Syngeneic B16F10 melanoma cells inoculated s.c. grew more rapidly in LT alpha(-/-) mice than in the wild-type littermates, and the formation of experimental pulmonary metastases was significantly enhanced in LT alpha(-/-) mice. Although LT alpha(-/-) mice exhibited almost a normal total number of NK cells in spleen, they showed an impaired recruitment of NK cells to lung and liver. Additionally, lytic NK cells were not efficiently produced from LT alpha(-/-) bone marrow cells in vitro in the presence of IL-2 and IL-15, These data suggest that LT alpha signaling may be involved in the maturation and recruitment of NK cells and may play an important role in antitumor surveillance. [References: 54]

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