Abstracts (complete list) - Wissenschaft Online

Daniela Wesch, Philine Wrobel, Hamed Shojaei, Hans-Heinrich Oberg, Monika Kunz,
Dieter Kabelitz
Implications for the design of γδ T cell-based cancer
immunotherapy
There is a substantial interest in γδ T cell-based cancer immunotherapy due to their
potent MHC-nonrestricted cytotoxicity towards various tumor cells. We analyzed the
susceptibility of a broad range of epithelial tumor cells to V9γVδ2 γδ T cell cytotoxicity.
The involvement of T cell receptor (TCR) and NKG2D-dependent recognition in tumor
cell recognition was characterized by antibody blockade. Our experiments revealed
three patterns of inhibition, i.e. preferential inhibition by anti-TCR antibody or anti-
NKG2D antibody, or the additive blockade by both antibodies. The extent of inhibition
did not correlate directly with the level of NKG2D ligand expression on epithelial tumor
cells. Further, our results indicate for the first time that the NKGD2 pathway is involved
in the lysis of different melanomas, squameous cell carcinomas of the head and neck
(SCCHN), lung carcinomas, and pancreatic adenocarcinomas. Lysis of poorly killed
tumor cells was enhanced by the pre-treatment of γδ T cells with TCR-stimulating
pyrophosphomonoesters or aminobisphosphonates. The enhancing effect by these
stimuli was independent of the degree of HLA (mis)match between target and effector.
Moreover, we currently investigate whether Toll-like receptor agonists, which are
suggested as adjuvant therapy in clinical trials for different types of cancer including
adenocarcinomas, have an influence on lysis of tumor cells by γδ T cells.
Our results indicate that tumors recognized independently of the TCR might be less
suited for γδ T cell immunotherapy with pyrophosphomonoesters or
aminobisphosphonates.
This study was supported by Werner and Klara Kreitz-Stiftung.