Proceedings for Annual Meeting of The Japanese Pharmacological Society
Online ISSN : 2435-4953
The 95th Annual Meeting of the Japanese Pharmacological Society
Session ID : 95_2-O-051
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NKG2D-high T cells are able to be activated regardless of the level of NKG2D ligands expression
*Hitoshi ToyodaMasahiro HosonumaAtsuo KuramasuYouichirou NarikawaMasakazu MurayamaJunya IsobeMidori ShidaTakehiko SambeMayumi TsujiTakuya TsunodaShinichi KobayashiKatsunori InagakiYuji KiuchiKiyoshi Yoshimura
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Abstract

Natural killer group 2 member D (NKG2D) expressed in natural killer (NK) cells and T cells is a receptor activated by NKG2D ligands such as MICA and MICB. In patients with gastric cancer, expression of NKG2D in tumor-infiltrating immune cells correlates with good prognosis. Because these tumor-infiltrating cells were mainly CD8+ T cells, we hypothesized that NKG2D+ T cells had proficient anti-tumor response. In the study, we investigated whether MICA or MICB activated T cells via NKG2D in vitro by using coculture system. Panc1, a human pancreatic cancer cell line, expressed MICA and MICB among eight NKG2D ligands. We sorted cells with low or high NKG2D expression from activated T cells and cocultured each of them with Panc1 cells that had been treated with siRNA of MICA and/or MICB.  After 3 days of coculture, we isolated T cells from coculture and measured interferon gamma (INFg) mRNA as an activation marker. INFg expression of NKG2Dlow T cells were augmented by downregulation of MICB, suggesting that MICB was a negative regulator.  In contrast, NKG2Dhigh T cells remained expressing INFg regardless of downregulation of MICA and/or MICB. These results suggest that NKG2Dhigh T cells were an elite population that could be activated independently of NKG2D ligands expression in cancer cells.

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