Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and tumor-infiltrating lymphocytes activated by PSK.
The protein-bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non-reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10-100 micrograms/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK-induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK-induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha-chain or beta-chain of IL-2 receptors (IL-2R) had no effect on PSK-induced ATK activity. Supernatants from PSK-stimulated lymphocyte cultures did not induce ATK. Cell fractionation experiments revealed that CD3-CD16+ large granular lymphocytes (LGL) and/or CD3+CD16- T lymphocytes were responsible for both spontaneous and PSK-induced ATK. PSK-activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL-2/IL-2R systems.
Department of Late Effect Studies, Kyoto University.
Y
Y
Kariya
N
N
Okamoto
T
T
Fujimoto
N
N
Inoue
T
T
Kihara
K
K
Sugie
M
M
Yagita
H
H
Kanzaki
T
T
Mori
A
A
Uchida
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016923:Cell Death; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011509:Proteoglycans / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology
D000903:Antibiotics, Antineoplastic; D007370:Interferon Type I; D007376:Interleukin-2; D011509:Proteoglycans; D011994:Recombinant Proteins; C010770:polysaccharide-K; D007371:Interferon-gamma