Abstract 3806: The pattern of NKG2DL expressions determines immunogenicity and antitumor effect of protein-bound polysaccharide-K in tumor-bearing mouse models

Background and Aim: Natural killer group 2, member D ligands (NKG2DLs) have paradoxical immunological characteristics, exerting both immune-stimulatory and immune-suppressive effects on T cell activation. First, we attempted to determine the relationship between the antitumor effect of protein-bound polysaccharide-K (PSK) in a tumor-bearing mouse model and the expression profile of NKG2DLs on a tumor. Next, we investigated whether NKG2DL expression on tumor cells affects T cell activation by examining the expression of NKG2D on and IFN-γ production in CD8+ T cells in mice bearing NKG2DL–expressing and NKG2DL–nonexpressing tumors.Materials and Methods: PSK was administered to evaluate its effectiveness against tumor growth. The expression of Rae-1 and H60 were analyzed in the cell lines. Results: PSK showed the highest antitumor effects in mice implanted with cells expressing neither Rae-1 nor H60. PSK had little antitumor effect in mice implanted with cells expressing both Rae-1 and H60. A correlation between the expression of NKG2DLs and the antitumor effect of PSK was observed. After PSK administration, INF-γ production in CD8+ T cells increased in mice with cells expressing neither Rae-1 nor H60, but did not change in mice implanted with cells expressing both Rae-1 and H60.Conclusion: we demonstrated that the expression pattern of NKG2DLs affects tumor immunity and the efficacy of immunotherapy in a tumor-bearing mouse model. In particular, the expression of H60 and Rae-1 family members may be an immunosuppressive factor. Further analysis is required to gain a better understanding of the mechanism of interaction between NKG2D expressed on immune effector cells and H60/Rae-1 expression on tumors. Although NKG2DL expression may represent a marker predicting response to immunotherapy, further studies in humans are required to validate this finding in the clinical setting. Citation Format: Tomohiro Takehara, Kenzo Soejima, Tomoko Betsuyaku, Kiyoshi Yoshimura. The pattern of NKG2DL expressions determines immunogenicity and antitumor effect of protein-bound polysaccharide-K in tumor-bearing mouse models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3806.