Background: Oesophageal and gastric cancers cause over 1.1 million deaths annually. Current therapeutic regimes focus on chemo-radiotherapy prior to surgery. However, only 20-30% of patients respond to treatment, therefore, new treatments are urgently required. iNKT cells are innate T cells with antitumour activity. In humans, they account for <1% of peripheral T cells but comprise ~10% of omental adipose tissue lymphocytes. We investigated the presence of iNKT cells in blood and omental tissue from gastrointestinal cancer patients. We also investigated if  systemic chemotherapies have adverse effects on iNKT cell functions.

Methods: iNKT cells were quantified in pre- and post-treatment blood and omentum from 89 patients with gastric cancer, SCC and OAC using flow cytometry. iNKT cells were isolated from human blood samples and expanded in vitro. iNKT cells from 4 donors were treated with various concentrations of cisplatin, carboplatin, paclitaxel and 5-fluorouracil, for 24 and 48 hrs. Cells were stained with annexin V and propidium iodide for cell death assays,  and co-cultured with CD1d transfected HeLa cells pulsed with α-GalCer, for assays of cytolytic degranulation and intracellular cytokine production.

Results: iNKT cells were found to be depleted from blood and omentum of cancer patients. No significant differences in iNKT cell numbers were observed between pre-treatment and post-treatment blood, from patients with OAC, SSC or gastric cancer. Cisplatin, 5-Fluorouralcil, carboplatin and paclitaxel exhibited a dose-dependent inhibition of iNKT cell viability. 5–fluorouracil and carboplatin inhibited degranulation by iNKT cells in co-culture with glycolipid-pulsed CD1d transfected HeLa cells. These doses of 5-fluorouracil and carboplatin also affected IFN-γ, but not IL-4 expression.

 Discussion: Low iNKT cell numbers may predispose individuals to upper gastrointestinal cancers.  Boosting of iNKT cell numbers may have therapeutic value. However, exposure to systemic chemotherapy can negatively affect their functions and should be considered when developing iNKT cell-based immunotherapies.