In vitro immunomodulating effect of protein-bound polysaccharide, PSK on peripheral blood, regional nodes, and spleen lymphocytes in patients with gastric cancer

Abstract

PSK, a protein-bound polysaccharide, has been widely used for cancer immunotherapy in Japan. However, the mechanism of its immunomodulatory effect has not been fully clarified. In the present study the in vitro effect of PSK on the lymphocytes of patients with gastric cancer was studied. Culturing lymphocytes with PSK at 5-100 micrograms/ml increased the level of DNA synthesis, and augmented the cytotoxicities against K562 and KATO-3. Flow-cytometric analysis also showed an increase in the proportion of interleukin-2 (IL-2)-receptor-positive cells after the lymphocytes were cultured with PSK. However the cytotoxicity of cells cultured with PSK was not augmented by the addition of recombinant interferon gamma (rIFN gamma) and rIL-2. Further experiments using fractionated PSK showed that its biological action is present mainly in fractions having molecular masses greater than 10(5) Da. However, these immunomodulations were not seen in all patients. These results suggest that the susceptibility of lymphocytes to PSK may be different in each patients, and that the immunomodulation by PSK may be mediated by mechanisms independent of IFN and IL-2.

A systematic review and meta-analysis of randomized trials on the role of targeted therapy in the management of advanced gastric cancer: Evidence does not translate?

“…Based on some experimental findings, it appears that an immune modulating effect should be considered even for mAbs used in aGC treatment. [80][81][82][83][84][85][86] Interestingly, in aGC, while bevacizumab did not demonstrate a significant benefit, indeed, in our analysis, we observed that trials evaluating other agents showed a highly significant efficacy in term of survival benefit in the anti-angiogenesis subgroup in aGC. 17,35,37 Several studies suggested that targeting VEGFR2 may elicit and improve the immune response directed toward the tumor and its microenvironment trough different mechanisms including direct activation of CD8 C cells and targeting of the FOXP3 high regulatory T cells.…”

Anticancer properties of polysaccharides isolated from fungi of the Basidiomycetes class

“…Increased numbers of immunologically competent cells and a rise in dendritic and Tc cells capacity of tumor infiltrate were noted in patients who received PSK. Krestin affects the phenotypic and functional maturation of dendritic cells from human CD14+ cells [61], and stimulates the phagocytic activity of macrophages [41]. In addition, it stimulates expression of TNF-α, IL-1, IL-6, and IL-8 [62–65].…”

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer

“…In vitro studies have confirmed that PSK induces the expression of several cytokine genes including TNF-α, IL-1, IL-1R, IL-2, IL-4, IL-6, IL-7, and IL-8 [12][13][14][15] . Anti-neoplastic effects of PSK have also been reported in animal models, and involve the radical trapping and modulation of cytokine production and effector cell functions [16,17] .…”