Effects of PSK on T and dendritic cells differentiation in gastric or colorectal cancer patients.
BACKGROUND
Vaccine therapy targeting tumor antigens recognized by cytotoxic T cells (CTL) has been tried extensively. However, in a cancer-bearing state, the Th1/Th2 balance shifts to Th2 dominance, and this has been the obstacle to vaccine therapy to induce the CTL. DC1/DC2 subsets have also been reported to control the differentiation of Th subsets. The key to tumor immunotherapy is how to activate the DC1-Th1 lineage.


METHODS
Six normal adults and 14 patients with gastric or colorectal cancers, who gave informed consent, were studied. The Th1/Th2 and DC1/DC2 ratios were determined by FACS. IL-12 and IL-10 production from PBMC were measured by ELISA.


RESULTS
The Th1/Th2 and DC1/DC2 ratios were all significantly lower in the patients with gastric or colorectal cancers compared to normal adults. After protein-bound polysaccharide K (PSK) therapy in cancer patients, the Th1/Th2 balance shifted to Th1 dominance and the DC1/DC2 balance to DC1 dominance. IL-10 production was significantly decreased by PSK therapy.


CONCLUSIONS
In the cancer-bearing state, the Th1/Th2 and DC/1/DC2 balance becomes Th2- and DC2-dominant. PSK therapy results in a shift of the Th1/Th2 and DC1/DC2 balance towards Th1 and DC1 dominance. We plan to examine whether combining dendritic cells (DC) vaccination therapy with oral PSK enhances the induction of T cell and DC differentiation in cancer patients.
Kanazawa
Masashi
M
Department of Surgery 2, Fukushima Medical University, Japan. Kanazawa@cc.fmu.ac.jp
Yoshihara
Kazue
K
Abe
Hiroyuki
H
Iwadate
Manabu
M
Watanabe
Kumiko
K
Suzuki
Satoshi
S
Endoh
Yoshiyuki
Y
Takita
Ken-Ichi
K
Sekikawa
Kouji
K
Takenoshita
Seiichi
S
Ogata
Takashi
T
Ohto
Hitoshi
H
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D019496:Cancer Vaccines; D019070:Cell Lineage; D002469:Cell Separation; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003713:Dendritic Cells / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000187:drug effects*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D019496:Cancer Vaccines; D011509:Proteoglycans; D016753:Interleukin-10; D018664:Interleukin-12; C010770:polysaccharide-K