Soluble branched (1,4)‐β‐D‐glucans from Acetobacter species enhance antitumor activities against MHC class I‐negative and ‐positive malignant melanoma through augmented NK activity and cytotoxic T‐cell response

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Abstract
We previously found that an extracellular polysaccharide, AC‐1, produced by Acetobacter polysaccharogenes composed of (1,4)‐β‐D‐glucan with branches of glucosyl residues showed a strong activity to induce production of interleukin (IL)‐12 p40 and tumor necrosis factor‐α by macrophage cell lines in vitro via Toll‐like receptor‐4 signaling. In the present study, we examined the effects of oral administration of AC‐1 on protection against 2 types of murine B16 melanoma lines, major histocompatibility complex (MHC) class I‐negative B16L and MHC class I gene‐transfected B16Kb cells. Mice were inoculated subcutaneously with B16L or B16Kb cells on day 0 and administrated intragastrically with AC‐1 or PBS once every 5 days from 1 day before tumor inoculation. The tumor growth was severely retarded in AC‐1‐treated mice after subcutaneous inoculation with B16L or B16Kb cells. The AC‐1‐treated mice showed augmented natural killer (NK) cell activity against B16L cells, and in vivo depletion of NK cells by antiasialoGM1 antibody (Ab) treatment abrogated the antitumor activity in AC‐1‐treated mice. On the other hand, AC‐1‐treated mice inoculated with B16Kb cells developed a significantly higher level of cytotoxic T‐lymphocyte response against B16Kb cells, and in vivo depletion of CD8+ T cells by anti‐CD8 mAb treatment abrogated the antitumor activity. Thus, AC‐1 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible prophylactic application of AC‐1 for human neoplasms irrespective of expression levels of their MHC class I molecules.