Top

Published in:

01-11-2008 | Original Article

Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling

Authors: Hirobumi Asai, Hiroko Iijima, Kenichi Matsunaga, Yoshiharu Oguchi, Hidetoshi Katsuno, Koutaro Maeda

Published in: Cancer Immunology, Immunotherapy | Issue 11/2008

Abstract

The protein-bound polysaccharide isolated from basidiomycetes (PSK), a biological response modifier, has been used as immunotherapeutic agent for the treatment of cancers. It has been demonstrated previously that PSK activates various types of immune cells in vitro, and orally administrated PSK activates anti-tumor CD4+ T cell response in mesenteric lymph nodes (MLNs). The detailed mechanism of action of PSK, however, has not been elucidated yet. The objective of the present study was to clarify the molecular mechanism of immunopotentiating effects of PSK using primary culture of the MLN CD4+ T cells. T cell receptor (TCR) stimulation-induced interleukin-2 production from MLN CD4+ T cells was significantly augmented by PSK in a concentration-dependent manner, and the augmentation was reflected at mRNA level. Furthermore, PSK augmented transcriptional activities of nuclear factor of activated T cells and activator protein 1, and phosphorylation of extracellular signal-regulated kinase 1/2 and linker for activation of T cells induced by TCR stimulation, whereas PSK had no influences without TCR stimulation. Collectively, the results indicate that PSK augments activation of MLN CD4+ T cells, probably by modulating the TCR signaling, and provide important knowledge for the elucidation of the true target molecule(s) of PSK.

Chu DH, Morita CT, Weiss A (1998) The Syk family of protein tyrosine kinases in T-cell activation and development. Immunol Rev 165:167–180PubMedCrossRef

Constant S, Pfeiffer C, Woodard A, Pasqualini T, Bottomly K (1995) Extent of T cell receptor ligation can determine the functional differentiation of naive CD4+ T cells. J Exp Med 182:1591–1596PubMedCrossRef

Croft M, Swain SL (1995) Recently activated naive CD4 T cells can help resting B cells, and can produce sufficient autocrine IL-4 to drive differentiation to secretion of T helper 2-type cytokines. J Immunol 154:4269–4282PubMed

Fisher M, Yang LX (2002) Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy. Anticancer Res 22:1737–1754PubMed

Franklin RA, Tordai A, Patel H, Gardner AM, Johnson GL, Gelfand EW (1994) Ligation of the T cell receptor complex results in activation of the Ras/Raf-1/MEK/MAPK cascade in human T lymphocytes. J Clin Invest 93:2134–2140PubMedCrossRef

García-Lora A, Pedrinaci S, Garrido F (2001) Protein-bound polysaccharide K and interleukin-2 regulate different nuclear transcription factors in the NKL human natural killer cell line. Cancer Immunol Immunother 50:191–8PubMedCrossRef

Harada M, Matsunaga K, Oguchi Y, Iijima H, Tamada K, Abe K, Takenoyama M, Ito O, Kimura G, Nomoto K (1997) Oral administration of PSK can improve the impaired anti-tumor CD4+ T-cell response in gut-associated lymphoid tissue (GALT) of specific-pathogen-free mice. Int J Cancer 70:362–372PubMedCrossRef

Hirai R, Oguchi Y, Sugita N, Matsunaga K, Nomoto K (1993) Enhancement of T-cell proliferation by PSK. Int J Immunopharmacol 15:745–750PubMedCrossRef

Hirose K, Zachariae CO, Oppenheim JJ, Matsushima K (1990) Induction of gene expression and production of immunomodulating cytokines by PSK in human peripheral blood mononuclear cells. Lymphokine Res 9:475–483PubMed

10.

Jain J, Loh C, Rao A (1995) Transcriptional regulation of the IL-2 gene. Curr Opin Immunol 7:333–342PubMedCrossRef

11.

Kanazawa M, Mori Y, Yoshihara K, Iwadate M, Suzuki S, Endoh Y, Ohki S, Takita K, Sekikawa K, Takenoshita S (2004) Effect of PSK on the maturation of dendritic cells derived from human peripheral blood monocytes. Immunol Lett 91:229–238PubMedCrossRef

12.

Komai-Koma M, Jones L, Ogg GS, Xu DM, Liew FY (2004) TLR2 is expressed on activated T cells as a costimulatory receptor. Proc Natl Acad Sci USA 101:3029–3034PubMedCrossRef

13.

Lewis RS (2001) Calcium signaling mechanisms in T lymphocytes. Annu Rev Immunol 19:497–521PubMedCrossRef

14.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMed

15.

Matsunaga K, Hosokawa A, Oohara M, Sugita N, Harada M, Nomoto K (1998) Direct action of a protein-bound polysaccharide, PSK, on transforming growth factor-beta. Immunopharmacology 40:219–230PubMedCrossRef

16.

Matsunaga K, Morita I, Oguchi Y, Fujii T, Yoshikumi C, Nomoto K (1987) The effect of a biological response modifier, PSK, on the intestinal immune system in tumor-bearing mice. Anticancer Res 7:509–512PubMed

17.

Nakazato H, Koike A, Saji S, Ogawa N, Sakamoto J (1994) Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer. Lancet 343:1122–1126PubMedCrossRef

18.

Noguchi K, Tanimura H, Yamaue H, Tsunoda T, Iwahashi M, Tani M, Mizobata S, Hotta T, Arii K, Tamai M, Terasawa H (1995) Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro. Anticancer Res 15:255–258PubMed

19.

Ohwada S, Ikeya T, Yokomori T, Kusaba T, Roppongi T, Takahashi T, Nakamura S, Kakinuma S, Iwazaki S, Ishikawa H, Kawate S, Nakajima T, Morishita Y (2004) Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study. Br J Cancer 90:1003–1010PubMedCrossRef

20.

Saito T, Yamasaki S (2003) Negative feedback of T cell activation through inhibitory adapters and costimulatory receptors. Immunol Rev 192:143–160PubMedCrossRef

21.

Samelson LE, O’Shea JJ, Luong H, Ross P, Urdahl KB, Klausner RD, Bluestone J (1987) T cell antigen receptor phosphorylation induced by an anti-receptor antibody. J Immunol 139:2708–2714PubMed

22.

Sathish JG, Walters J, Luo JC, Johnson KG, Leroy FG, Brennan P, Kim KP, Gygi SP, Neel BG, Matthews RJ (2004) CD22 is a functional ligand for SH2 domain-containing protein-tyrosine phosphatase-1 in primary T cells. J Biol Chem 279:47783–47791PubMedCrossRef

23.

Swain SL, Bradley LM, Croft M, Tonkonogy S, Atkins G, Weinberg AD, Duncan DD, Hedrick SM, Dutton RW, Huston G (1991) Helper T-cell subsets: phenotype, function and the role of lymphokines in regulating their development. Immunol Rev 123:115–144PubMedCrossRef

24.

Vanky F, Wang P, Klein E (1992) The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumor cells. Cancer Immunol Immunother 35:193–198PubMedCrossRef

25.

Wange RL, Samelson LE (1996) Complex complexes: signaling at the TCR. Immunity 5:197–205PubMedCrossRef

26.

Yamasaki S, Nishida K, Hibi M, Sakuma M, Shiina R, Takeuchi A, Ohnishi H, Hirano T, Saito T (2001) Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules. J Biol Chem 276:45175–45183PubMedCrossRef

27.

Yefenof E, Gafanovitch I, Oron E, Bar M, Klein E (1995) Prophylactic intervention in radiation-leukemia-virus-induced murine lymphoma by the biological response modifier polysaccharide K. Cancer Immunol Immunother 41:389–396PubMedCrossRef

28.

Zhang H, Morisaki T, Matsunaga H, Sato N, Uchiyama A, Hashizume K, Nagumo F, Tadano J, Katano M (2000) Protein-bound polysaccharide PSK inhibits tumor invasiveness by down-regulation of TGF-beta1 and MMPs. Clin Exp Metastasis 18:343–352PubMed

29.

Zhang J, Somani AK, Siminovitch KA (2000) Roles of the SHP-1 tyrosine phosphatase in the negative regulation of cell signaling. Semin Immunol 12:361–378PubMedCrossRef

30.

Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE (2000) Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. J Biol Chem 275:23355–23361PubMedCrossRef

Title: Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling
Authors: Hirobumi Asai
Hiroko Iijima
Kenichi Matsunaga
Yoshiharu Oguchi
Hidetoshi Katsuno
Koutaro Maeda
Publication date: 01-11-2008
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 11/2008
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-008-0498-1

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 11/2008

Cooperation of adenosine and prostaglandin E2 (PGE2) in amplification of cAMP–PKA signaling and immunosuppression

The “A, B and C” of Her-2 DNA vaccine development

Oncoantigens as anti-tumor vaccination targets: the chance of a lucky strike?

Molecular mechanisms of MHC class I abnormalities and APM components in human tumors

Inefficient presentation of tumor-derived antigen by tumor-infiltrating dendritic cells

Cancer treatment: the combination of vaccination with other therapies

Keynote webinar | Spotlight on antibody–drug conjugates in cancer