Enhancement of anti-tumor immunity by lipoteichoic acid-related molecule isolated from OK-432, a streptococcal agent, in athymic nude mice bearing human salivary adenocarcinoma: role of natural killer cells.
BACKGROUND
OK-PSA, a lipoteichoic acid (LTA)-related molecule isolated from a streptococcal agent OK-432, enhances anti-tumor immunity as a potent inducer of Th1-type cytokines. Recently, we obtained the data suggesting that natural killer (NK) cells may play a significant role for OK-PSA-induced cytokine production in vitro.


METHODS
We conducted the animal experiments using athymic nude mice bearing human salivary adenocarcinoma to examine the role of NK cells in OK-PSA-induced anti-tumor immunity. OK-PSA was peritumorally injected into the mice. Cytokines in the sera were analyzed by ELISA. mRNAs for cytokines were detected by RT-PCR. 51Cr release test was performed to measure killer cell activities.


RESULTS
OK-PSA markedly increased the amounts of IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18 that are generally called "Th1-type cytokines" in the sera derived from tumor-bearing nude mice, and also accelerated the killing activities of tumor-infiltrating lymphocytes as well as of draining lymph node cells. Furthermore, OK-PSA administration resulted in significant inhibition of tumor growth, but the effect of OK-PSA was almost completely inhibited by the deletion of NK cells using anti-asialo GM1 antibody.


CONCLUSIONS
These findings strongly suggested that NK cells are closely involved in OK-PSA-mediated anti-tumor immunity.
Okamoto
Masato
M
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho, Tokushima 7708504, Japan.
Ohe
Go
G
Furuichi
Sachiko
S
Nishikawa
Hidetomo
H
Oshikawa
Tetsuya
T
Tano
Tomoyuki
T
Ahmed
Sharif Uddin
SU
Yoshida
Hideo
H
Moriya
Yoichiro
Y
Matsubara
Shuzo
S
Ryoma
Yoshiki
Y
Saito
Motoo
M
Sato
Mitsunobu
M
D000230:Adenocarcinoma / Q000276:immunology* / Q000532:radiotherapy / Q000628:therapy*; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D005677:G(M1) Ganglioside / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D010844:Picibanil / Q000737:chemistry; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000276:immunology* / Q000532:radiotherapy / Q000628:therapy*; D013682:Teichoic Acids / Q000276:immunology / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013682:Teichoic Acids; D009569:Nitric Oxide; D005677:G(M1) Ganglioside; D010844:Picibanil; C009900:lipoteichoic acid; C018835:asialo GM1 ganglioside; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse