B7-H6 as an efficient target for T cell-induced cytotoxicity in haematologic malignant cells.

T cells play crucial roles in the antitumour immune response. However, their dysfunction leads to inefficient tumour eradication. New members of the B7 family have moved to the fore of cancer research because of their involvement in T cell-mediated immune escape and tumorigenesis. Recently, bispecific antibodies (Bi-Abs) have become attractive because of their ability to activate T cells to target tumours. In this study, we examined the expression of new B7 family members B7-H4, B7-H5, B7-H6, and B7-H7 in human haematological tumour cells. Furthermore, we explored whether B7-H6 is an efficient target for T cell-induced cytotoxicity in haematologic malignant cells. We determined the capability of T cells armed with the bispecific antibody anti-CD3 × anti-B7-H6 (B7-H6Bi-Ab) to target haematological tumours in K562, Thp-1, Daudi, Jurkat, and U266 cells. Compared with their T cell counterparts, B7-H6Bi-Ab-armed T cells demonstrated significant cytotoxicity induction in B7-H6+ haematological tumour cells, according to quantitative luciferase and lactate dehydrogenase assays, and their activity was accompanied by increased levels of the secreted killing mediators granzyme B and perforin. Moreover, B7-H6Bi-Ab-armed T cells produced more T cell-derived cytokines: TNF-α, IFN-γ, and IL-2. In addition, compared to the control T cells, a higher level of the activation marker CD69 was detected on the B7-H6Bi-Ab-armed T cells. Taken together, these data suggest that the antitumour effect of B7-H6Bi-Ab-armed T cells may be a promising immunotherapy for use in future haematologic treatments.

[Mechanistic study of nimesulide on enhancing gammadeltaT cell-mediated killing of gastric cancer cells].

AIM: To explore the effect of nimesulide on human gammadeltaT cell function. METHODS: gammadeltaT cells were cultured routinely, collected on the 9th day, and then induced with nimesulide at indicated concentrations (0.25 micromol/L, 0.5 micromol/L, 1 micromol/L, 2 micromol/L, 4 micromol/L, respectively). Twenty-four hours after induction, the supernatants were collected to detect IFN-gamma, TNF-alpha and IL-12, whereas the cells were assayed for perforin, granzyme B and NKG2D by flow cytometry (FCM) and for killing of gastric cancer cells by LDH. RESULTS: Nimesulide (1 micromol/L) caused gammadeltaT cells to express more of perforin and granzyme B (62.8% and 72.7%, respectively) than the control group (51.4% and 60.9%, respectively) (P<0.05). Likewise, nimesulide (1 micromol/L) enabled gammadeltaT cells to secret more of IFN-gamma and TNF-alpha (262.3 ng/L and 177.5 ng/L, respectively) than the control group (196.1 ng/L and 158.5 ng/L, respectively) (P<0.05). Nimesulide did not affect IL-12 secreting capability of gammadeltaT cells as compared with the control group (P>0.05). Nimesulide-stimulated gammadeltaT cells killed more of SGC-7901 and BCG-823 gastric cancer cells (73% and 70%, respectively) than the control group(54% and 53%, respectively) (P<0.05). CONCLUSION: Nimesulide made gammadeltaT cells to express more perforin and granzyme B and to secret more IFN-gamma and TNF-alpha into the supernatant, leading to higher killing rate of SGC-7901 and BCG-823 gastric cancer cells. The above data provides experimental basis on the clinical use of nimesulide to prevent and treat digestive tract tumors.