Background In recent years there has been increasing evidence highlighting biochemical pathways operated by human cancer cells, which allow them to escape host immune surveillance. Understanding the molecular basis of these immune evasion pathways and mechanisms underlying their biochemical regulation would allow development of fundamentally novel strategies of anti-cancer immunotherapy. This work is devoted to understanding the pathological role of Tim-3-galectin-9 immunosuppressive pathway.

Materials and Methods To complete this work we used human cancer and non-malignant cell lines as well as primary human malignant liquid (leukaemia) and solid tumour samples. We also used human primary natural killer (NK) cells and TALL-104 cytotoxic T cell line. Western blot analysis, on-cell and in-cell Western analysis, ELISA, quantitative real-time PCR, flow cytometry (including imaging flow cytometry) and biochemical enzyme activity were used as research tools.

Results We found that galectin-9 is highly expressed in human liquid (acute myeloid leukaemia (AML) and solid (breast, colorectal, brain etc.) tumour cells. G protein-coupled receptors of latrophilin family and their natural ligand fibronectin leucine rich transmembrane protein 3 (FLRT3) trigger externalisation/exocytosis, and, in some cases (e. g. AML), biosynthesis of galectin-9 and its receptor and possible trafficker Tim-3. Galectin-9 can be used to suppress anti-cancer immune responses by impairing cytotoxic activity of NK cells and killing T cells.

Conclusions We report the Tim-3-galectin-9 secretory pathway as one of the biochemical mechanisms operated by human cancer cells to escape host immune surveillance. Differential activities based on cell type of origin are discussed.

Disclosure Information I.M. Yasinska: None. E. Klenova: None. E. Klenova Fasler-Kan: None. V. Sumbayev: None.