Potential role of natural killer cells in controlling growth and infiltration of AIDS-associated primary effusion lymphoma cells.
Natural killer (NK) cells are an important component of the innate immune response against microbial infections and tumors. Direct involvement of NK cells in tumor growth and infiltration has not yet been demonstrated clearly. Primary effusion lymphoma (PEL) cells were able to produce tumors and ascites very efficiently with infiltration of cells in various organs of T-, B- and NK-cell knock-out NOD/SCID/gammac(null) (NOG) mice within 3 weeks. In contrast, PEL cells formed small tumors at inoculated sites in T- and B-cell knock-out NOD/SCID mice with NK-cells while completely failing to infiltrate into various organs. Immunosupression of NOD/SCID by treatment with an antimurine TM-beta1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanced tumorigenicity and organ infiltration in comparison with non-treated NOD/SCID mice. Activated human NK cells inhibited tumor growth and infiltration in NOG mice. Our results suggest that NK cells play an important role in growth and infiltration of PEL cells, and activated NK cells could be a promising immunotherapeutic tool against tumor or virus-infected cells either alone or in combination with conventional therapy. The rapid and efficient engraftment of PEL cells in NOG mice also suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of pathogenesis and malignant cell growth.
Dewan
Md Zahidunnabi
MZ
Department of Molecular Virology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Terunuma
Hiroshi
H
Toi
Masakazu
M
Tanaka
Yuetsu
Y
Katano
Harutaka
H
Deng
Xuewen
X
Abe
Hiroyuki
H
Nakasone
Tadashi
T
Mori
Naoki
N
Sata
Tetsutaro
T
Yamamoto
Naoki
N
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured / Q000473:pathology / Q000637:transplantation / Q000821:virology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D007124:Immunoenzyme Techniques; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D008212:Lymphocyte Depletion; D016246:Lymphocytes, Tumor-Infiltrating; D008223:Lymphoma / Q000276:immunology / Q000628:therapy* / Q000821:virology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000209:etiology / Q000473:pathology / Q000628:therapy; D016066:Pleural Effusion, Malignant / Q000276:immunology / Q000628:therapy* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*