Oral beta-glucan adjuvant therapy converts nonprotective Th2 response to protective Th1 cell-mediated immune response in mammary tumor-bearing mice.
Beta (1-3)-D-glucans were identified almost 40 years ago as biological response modifiers that stimulated tumor rejection. In vitro studies have shown that beta-glucans bind to a lectin domain within complement receptor type 3 (CR3), or to, more recently described dectin-1 a beta-glucan specific receptor, acting mainly on phagocytic cells. In this study, we assessed the intracellular cytokine profiles of peripheral blood lymphocytes from mice bearing mammary tumors receiving i.v. anti-tumor mAbs combined or not with whole glucan particle suspension given orally (WGP, 400 microg every 24 hours). The proportions of T cells producing IL-4 and IFNgamma were determined by flow cytometry. The proportion of T cells producing IL-4 was significantly higher in tumor-bearing mice not receiving beta-glucan-enhanced therapy. Conversely, T cells from mice undergoing beta-glucan-enhanced therapy showed increased production of the Th1 cytokine IFNgamma. The switch from a Th2 to a Th1 response after WGP therapy was possibly mediated by intestinal mucosal macrophages releasing IL-12.
Baran
Jarek
J
Tumor Immunobiology Program, James Graham Brown Cancer Center, University of Louisville, KY, USA. mibaran@cyf-kr.edu.pl
Allendorf
Daniel J
DJ
Hong
Feng
F
Ross
Gordon D
GD
D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017024:Chemotherapy, Adjuvant; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology*; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008264:Macrophages / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D047071:beta-Glucans / Q000008:administration & dosage* / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D047071:beta-Glucans; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma